Search

Exhausted CD8 T (T ex ) cells in chronic viral infection and cancer have sustained co-expression of inhibitory receptors (IRs). T ex cells can be reinvigorated by blocking IRs, such as PD-1, but synergistic reinvigoration and enhanced disease control can be achieved by co-targeting multiple IRs including PD-1 and LAG-3. To dissect the molecular changes intrinsic when these IR pathways are disrupted, we investigated the impact of loss of PD-1 and/or LAG-3 on T ex cells during chronic infection. These analyses revealed distinct roles of PD-1 and LAG-3 in regulating T ex cell proliferation and effector functions, respectively. Moreover, these studies identified an essential role for LAG-3 in sustaining TOX and T ex cell durability as well as a LAG-3-dependent circuit that generated a CD94/NKG2 + subset of T ex cells with enhanced cytotoxicity mediated by recognition of the stress ligand Qa-1b, with similar observations in humans. These analyses disentangle the non-redundant mechanisms of PD-1 and LAG-3 and their synergy in regulating T ex cells., Competing Interests: Declaration of interests E.J.W. is a member of the Parker Institute for Cancer Immunotherapy which supported this study. E.J.W. is an advisor for Arsenal Bioscience, Coherus, Danger Bio, Janssen, New Limit, Marengo, Pluto Immunotherapeutics, Prox Biosciences, Related Sciences, Santa Ana Bio, and Synthekine. E.J.W. is a founder of and holds stock in Arsenal Biosciences. A.H.S. has patents/pending royalties on the PD-1 pathway from Roche and Novartis and has research funding from IOME, AbbVie, and Taiwan Bio. A.H.S. serves as an advisor for Selecta, Elpiscience, Monopteros, Bicara, Fibrogen, IOME, Bioentre, Corner Therapeutics, Alixia, GlaxoSmithKline, Amgen, and Janssen. D.A.A.V. has patents covering LAG-3, with others pending. D.A.A.V. is a co-founder and stockholder for Novasenta, Tizona, and Trishula; a stockholder for Oncorus and Werewolf; and has patents licensed to Bristol Myers Squibb (BMS) and Novasenta. D.A.A.V. is a scientific advisor for Tizona, Werewolf, F-Star, Bicara, Apeximmune, and T7/Imreg Bio and is a consultant for BMS, Incyte, Regeneron, Ono Pharma, Peptone, and Avidity Partners. D.A.A.V. receives research funding from BMS and Novasenta. O.K. holds stock in Arsenal Biosciences and is an employee of Orange Grove Bio. A.C.H. consults for Immunai and received research funding from BMS and Merck. J.R.G. consults for Arsenal Biosciences., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: This study investigated shame-proneness as a moderating risk factor within the relationship between perceived discrimination and mental health outcomes. Moderation across race, gender, and race-by-gender intersections was also examined., Method: Bayesian analysis was employed to examine moderation among African, Latinx, and Asian descent college students ( N = 295)., Results: Shame-proneness had a moderating role contingent on participants' social identities. Higher shame-proneness moderated the discrimination-anxiety relationship for the African American sample and African American women and moderated the discrimination-depression relationship for African American women and men, respectively., Conclusions: The present study advances our understanding of the association between discrimination and negative mental health outcomes. African American participants with high shame-proneness were uniquely impacted by discrimination. Researchers, clinicians, and university officials are encouraged to develop culturally informed interventions and services to support this population. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

ESR1 mutation ( ESR1 m) is a frequent cause of acquired resistance to aromatase inhibitor (AI) plus cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i), which is a first-line therapy for hormone-receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). Camizestrant is a next-generation oral selective estrogen receptor degrader (SERD) that in a phase II study significantly improved progression-free survival (PFS) over fulvestrant (also a SERD) in ER+/HER2- ABC. SERENA-6 (NCT04964934) is a randomized, double-blind, phase III study evaluating the efficacy and safety of switching from an AI to camizestrant, while maintaining the same CDK4/6i, upon detection of ESR1 m in circulating tumor DNA before clinical disease progression on first-line therapy for HR+/HER2- ABC. The aim is to treat ESR1 m clones and extend the duration of control of ER-driven tumor growth, delaying the need for chemotherapy. The primary end point is PFS; secondary end points include chemotherapy-free survival, time to second progression event (PFS2), overall survival, patient-reported outcomes and safety.

This descriptive case series retrospectively reviewed medical records from thirty-one previously healthy, war-fighting veterans who self-reported exposure to airborne hazards while serving in Iraq and Afghanistan between 2003 and the present. They all noted new-onset dyspnea, which began during deployment or as a military contractor. Twenty-one subjects underwent non-invasive pulmonary diagnostic testing, including maximum expiratory pressure (MEP) and impulse oscillometry (IOS). In addition, five soldiers received a lung biopsy; tissue results were compared to a previously published sample from a soldier in our Iraq Afghanistan War Lung Injury database and others in our database with similar exposures, including burn pits. We also reviewed civilian control samples (5) from the Stony Brook University database. Military personnel were referred to our International Center of Excellence in Deployment Health and Medical Geosciences, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell under the auspices of Northwell IRB: 17-0140-FIMR Feinstein Institution for Medical Research "Clinicopathologic characteristics of Iraq Afghanistan War Lung Injury." We retrospectively examined medical records, including exposure data, radiologic imaging, and non-invasive pulmonary function testing (MGC Diagnostic Platinum Elite Plethysmograph) using the American Thoracic Society (ATS) standard interpretation based on Morgan et al., and for a limited cohort, biopsy data. Lung tissue, when available, was examined for carbonaceous particles, polycyclic aromatic hydrocarbons (Raman spectroscopy), metals, titanium connected to iron (Brookhaven National Laboratory, National Synchrotron Light Source II, Beamline 5-ID), oxidized metals, combustion temperature, inflammatory cell accumulation and fibrosis, neutrophil extracellular traps, Sirius red, Prussian Blue, as well as polarizable crystals/particulate matter/dust. Among twenty-one previously healthy, deployable soldiers with non-invasive pulmonary diagnostic tests, post-deployment, all had severely decreased MEP values, averaging 42% predicted. These same patients concurrently demonstrated abnormal airways reactance (X5Hz) and peripheral/distal airways resistance (D5-D20%) via IOS, averaging - 1369% and 23% predicted, respectively. These tests support the concept of airways hyperresponsiveness and distal airways narrowing, respectively. Among the five soldiers biopsied, all had constrictive bronchiolitis. We detected the presence of polycyclic aromatic hydrocarbons (PAH)-which are products of incomplete combustion-in the lung tissue of all five warfighters. All also had detectable titanium and iron in the lungs. Metals were all oxidized, supporting the concept of inhaling burned metals. Combustion temperature was consistent with that of burned petrol rather than higher temperatures noted with cigarettes. All were nonsmokers. Neutrophil extracellular traps were reported in two biopsies. Compared to our prior biopsies in our Middle East deployment database, these histopathologic results are similar, since all database biopsies have constrictive bronchiolitis, one has lung fibrosis with titanium bound to iron in fixed mathematical ratios of 1:7 and demonstrated polarizable crystals. These results, particularly constrictive bronchiolitis and polarizable crystals, support the prior data of King et al. (N. Engl. J. Med. 365:222-230, 2011) Soldiers in this cohort deployed to Iraq and Afghanistan since 2003, with exposure to airborne hazards, including sandstorms, burn pits, and improvised explosive devices, are at high risk for developing chronic clinical respiratory problems, including: (1) reduction in respiratory muscle strength; (2) airways hyperresponsiveness; and (3) distal airway narrowing, which may be associated with histopathologic evidence of lung damage, reflecting inhalation of burned particles from burn pits along with particulate matter/dust. Non-invasive pulmonary diagnostic tests are a predictor of burn pit-induced lung injury., (© 2022. The Author(s).)

Background: With laser irradiation emerging as an adjunctive treatment utilized in nonsurgical periodontal therapy, it is important to understand the variance of penetration depth among the different laser wavelengths. Purpose: To evaluate the thermal penetration depth, as a photothermal effect, of carbon dioxide (CO 2 )-, erbium: doped yttrium-aluminum-garnett (Er:YAG)-, and erbium, chromium: yttrium-scandium-gallium-garnett (Er,Cr:YSGG)-lasers on the bovine gingiva in an in vitro model. Methods: Four mandibles from freshly slaughtered cows were utilized in this study. Buccal and lingual root debridement was provided using three different laser wavelengths, all in pulsed settings. A CO 2 - (10,600 nm), Er:YAG- (2940 nm), and Er,Cr:YSGG- (2780 nm) were utilized to irradiate pockets of two mandibular posterior teeth in each group. Laser power output settings were set to 2 W. The posterior teeth were irradiated for 30 sec buccal and 30 sec lingual of each tooth for all selected treatment test groups. Instrumentation with curettes was performed as a control group. Gingival flaps, including the entire gingiva, were fixed in 10% formalin and stained via Elastin van Gieson. Sections were examined microscopically to evaluate thermal damage and statistically compared using mixed effect model with Tukey adjustment. Results: The CO 2 -laser irradiation presented a statistically significant lower mean compared to Er,Cr:YSGG-laser ( p  < 0.0001). Er,Cr:YSGG-laser had a higher penetration depth compared to Er:YAG-laser ( p  < 0.0001). There was no statistically significant difference found in penetration depth between CO 2 - and Er:YAG-laser irradiation. Conclusions: It can be concluded that all tested pulsed lasers had minimal penetration depth into the gingiva. However, the pulsed CO 2 - and Er:YAG-lasers presented lower thermal effects compared to Er,Cr:YSGG-laser in vitro .

Motivation: The availability of databases identifying allergenic proteins via a transparent and consensus-based scientific approach is of prime importance to support the safety review of genetically-modified foods and feeds, and public safety in general. Over recent years, screening for potential new allergens sequences has become more complex due to the exponential increase of genomic sequence information. To address these challenges, an international collaborative scientific group coordinated by the Health and Environmental Sciences Institute (HESI), was tasked to develop a contemporary, adaptable, high-throughput process to build the COM prehensive P rotein A llergen RE source (COMPARE) database, a publicly accessible allergen sequence data resource along with bioinformatics analytical tools following guidelines of FAO/WHO and CODEX Alimentarius Commission. Results: The COMPARE process is novel in that it involves the identification of candidate sequences via automated keyword-based sorting algorithm and manual curation of the annotated sequence entries retrieved from public protein sequence databases on a yearly basis; its process is meant for continuous improvement, with updates being transparently documented with each version; as a complementary approach, a yearly key-word based search of literature databases is added to identify new allergen sequences that were not (yet) submitted to protein databases; in addition, comments from the independent peer-review panel are posted on the website to increase transparency of decision making; finally, sequence comparison capabilities associated with the COMPARE database was developed to evaluate the potential allergenicity of proteins, based on internationally recognized guidelines, FAO/WHO and CODEX Alimentarius Commission., Competing Interests: LB was employee of Limagrain Field Seeds. EI was employee of BASF Corporation. GL was employee of DuPont Co., Nutrition and Biosciences. SM was employee of Syngenta Crop protection. AS was employee of Bayer Crop Science. PS was employee of Corteva Agriscience LLC. CB was employed by Bayer Crop Science. GS was employed by company IFF Inc. 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 © 2021 van Ree, Sapiter Ballerda, Berin, Beuf, Chang, Gadermaier, Guevera, Hoffmann-Sommergruber, Islamovic, Koski, Kough, Ladics, McClain, McKillop, Mitchell-Ryan, Narrod, Pereira Mouriès, Pettit, Poulsen, Silvanovich, Song, Teuber and Bowman.)

Background: Food proteins differ in their allergenic potential. Currently, there is no predictive and validated bio-assay to evaluate the allergenicity of novel food proteins. The objective of this study was to investigate the potential of a human peripheral blood mononuclear cell (PBMC) gene expression assay to identify biomarkers to predict the allergenicity of legume proteins., Results: PBMCs from healthy donors were exposed to weakly and strongly allergenic legume proteins (2S albumins, and 7S and 11S globulins from white bean, soybean, peanut, pea and lupine) in three experiments. Possible biomarkers for allergenicity were investigated by exposing PBMCs to a protein pair of weakly (white bean) and strongly allergenic (soybean) 7S globulins in a pilot experiment. Gene expression was measured by RNA-sequencing and differentially expressed genes were selected as biomarkers. 153 genes were identified as having significantly different expression levels to the 7S globulin of white bean compared to soybean. Inclusion of multiple protein pairs from 2S albumins (lupine and peanut) and 7S globulins (white bean and soybean) in a larger study, led to the selection of CCL2, CCL7, and RASD2 as biomarkers to distinguish weakly from strongly allergenic proteins. The relevance of these three biomarkers was confirmed by qPCR when PBMCs were exposed to a larger panel of weakly and strongly allergenic legume proteins (2S albumins, and 7S and 11S globulins from white bean, soybean, peanut, pea and lupine)., Conclusions: The PBMC gene expression assay can potentially distinguish weakly from strongly allergenic legume proteins within a protein family, though it will be challenging to develop a generic method for all protein families from plant and animal sources. Graded responses within a protein family might be of more value in allergenicity prediction instead of a yes or no classification.

Doravirine, a novel nonnucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus 1 (HIV-1), is predominantly cleared by cytochrome P450 (CYP) 3A4 and metabolized to an oxidative metabolite (M9). Coadministration with rifabutin, a moderate CYP3A4 inducer, decreased doravirine exposure. Based on nonparametric superposition modeling, a doravirine dose adjustment from 100 mg once daily to 100 mg twice daily during rifabutin coadministration was proposed. However, M9 exposure may also be impacted by induction, in addition to the dose adjustment. As M9 concentrations have not been quantified in previous clinical studies, a physiologically based pharmacokinetic model was developed to investigate the change in M9 exposure when doravirine is coadministered with CYP3A inducers. Simulations demonstrated that although CYP3A induction increases doravirine clearance by up to 4.4-fold, M9 exposure is increased by only 1.2-fold relative to exposures for doravirine 100 mg once daily in the absence of CYP3A induction. Thus, a 2.4-fold increase in M9 exposure relative to the clinical dose of doravirine is anticipated when doravirine 100 mg twice daily is coadministered with rifabutin. In a subsequent clinical trial, doravirine and M9 exposures, when doravirine 100 mg twice daily was coadministered with rifabutin, were found to be consistent with model predictions using rifampin and efavirenz as representative inducers. These findings support the dose adjustment to doravirine 100 mg twice daily when coadministered with rifabutin., (© 2020, The American College of Clinical Pharmacology.)

Background: Adolescent and young adults (AYA) with Type 1 Diabetes (T1D) experience more difficulty with glycemic control than patients in all other age groups. The shared medical appointment (SMA) model has been effective in multiple healthcare populations, but the feasibility and effectiveness of SMA in AYA patients with T1D is unclear., Methods: This research leverages the team's multidisciplinary expertise to develop an engaging intervention toolkit and test the implementation of the Team Clinic care model for the treatment of T1D among middle school adolescents in a large urban children's hospital serving an economically, racially and ethnically diverse population. In Phase 1, the team will manualize the Team Clinic care model into an engaging, age-appropriate educational and intervention toolkit. In Phase 2, the team will conduct a randomized clinical trial to test the feasibility and usability of the toolkit from the provider perspective (team member satisfaction; clinical efficiency; compliance with American Diabetes Association, American Association of Diabetes Educators, and California Children's Services standards; and payor-level cost data) and the preliminary efficacy of the intervention toolkit on patient- and family-level outcomes (attendance, acceptability/satisfaction with care, patient-level cost data, diabetes outcomes, diabetes family conflict, diabetes distress, and depression)., Discussion: AYA patients with T1D often receive care in clinics and institutions with limited resources and time. This research tests the feasibility and efficacy of an innovative and potentially cost-effective SMA model to address the unique needs of underserved populations, while meeting national and state clinical standards. Trial registration The study is registered with ClinicalTrials.gov (Protocol Record: NCT04190368)., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest or competing interests pertinent to this study. The authors have no financial relationships relevant to this article to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Alternative and sustainable protein sources (e.g., algae, duckweed, insects) are required to produce (future) foods. However, introduction of new food sources to the market requires a thorough risk assessment of nutritional, microbial and toxicological risks and potential allergic responses. Yet, the risk assessment of allergenic potential of novel proteins is challenging. Currently, guidance for genetically modified proteins relies on a weight-of-evidence approach. Current Codex (2009) and EFSA (2010; 2017) guidance indicates that sequence identity to known allergens is acceptable for predicting the cross-reactive potential of novel proteins and resistance to pepsin digestion and glycosylation status is used for evaluating de novo allergenicity potential. Other physicochemical and biochemical protein properties, however, are not used in the current weight-of-evidence approach. In this study, we have used the Random Forest algorithm for developing an in silico model that yields a prediction of the allergenic potential of a protein based on its physicochemical and biochemical properties. The final model contains twenty-nine variables, which were all calculated using the protein sequence by means of the ProtParam software and the PSIPred Protein Sequence Analysis program. Proteins were assigned as allergenic when present in the COMPARE database. Results show a robust model performance with a sensitivity, specificity and accuracy each greater than ≥85%. As the model only requires the protein sequence for calculations, it can be easily incorporated into the existing risk assessment approach. In conclusion, the model developed in this study improves the predictability of the allergenicity of new or modified food proteins, as demonstrated for insect proteins., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The calcaneal fat pad is a major load bearing component of the human foot due to daily gait activities such as standing, walking, and running. Heel and arch pain pathologies such as plantar fasciitis, which over one third of the world population suffers from, is a consequent effect of calcaneal fat pad damage. Also, fat pad stiffening and ulceration has been observed due to diabetes mellitus. To date, the biomechanics of fat pad damage is poorly understood due to the unavailability of live human models (because of ethical and biosafety issues) or biofidelic surrogates for testing. This also precludes the study of the effectiveness of preventive custom orthotics for foot pain pathologies caused due to fat pad damage. The current work addresses this key gap in the literature with the development of novel biofidelic surrogates， which simulate the in vivo and in vitro compressive mechanical properties of a healthy calcaneal fat pad. Also, surrogates were developed to simulate the in vivo mechanical behavior of the fat pad due to plantar fasciitis and diabetes. A four-part elastomeric material system was used to fabricate the surrogates, and their mechanical properties were characterized using dynamic and cyclic load testing. Different strain (or displacement) rates were tested to understand surrogate behavior due to high impact loads. These surrogates can be integrated with a prosthetic foot model and mechanically tested to characterize the shock absorption in different simulated gait activities, and due to varying fat pad material property in foot pain pathologies (i.e., plantar fasciitis, diabetes, and injury). Additionally, such a foot surrogate model, fitted with a custom orthotic and footwear, can be used for the experimental testing of shock absorption characteristics of preventive orthoses.

Platelet-rich plasma (PRP) derived from autologous peripheral blood is rich in platelets that release growth factors and cytokines. We determined the effects of topically applied autologous PRP in a partial thickness porcine burn model. Partial thickness burns were created on the backs and flanks of six domestic pigs (24 burns each) using an aluminium bar preheated to 80° C for 20 seconds. After removing the necrotic epidermis, the burns were randomly treated with a topical antibiotic ointment or a single (day 2), double (days 2 and 7), or triple (days 2, 7, and 14) topical application of PRP that was prepared freshly before application. Periodic imaging and full thickness biopsies were conducted to monitor healing over 28 days. The percentage wound reepithelialization at days 11, 14, 18 and 21 did not differ significantly among the groups. By day 28 all wounds were completely (>95%) reepithelialized, and there were no differences among the groups. Time to complete healing (presented as mean, [SD]) did not differ among the groups (antibiotics, 17.1 [3.5]; single PRP, 17.6 [4.0]; double PRP, 18.4 [3.9]; and triple PRP, 17.7 [3.3] days; ANOVA P=0.43). Scar depth (presented as mean, [SD]) in mm at day 28 by treatment group was: antibiotic 5.0 [1.0], single PRP 5.5 [1.1], double PRP 5.4 [1.1], and triple PRP 5.5 [0.6], ANOVA P=0.026. We conclude that PRP results in similar rates of reepithelialization and scar depth to standard topical antibiotics in a partial thickness porcine burn model.

Introduction: Platelet rich plasma (PRP) is rich in growth factors and has been shown to improve healing in a variety of wounds. We determined the effects of PRP on healing and scarring in full thickness porcine burns with and without tangential excision and grafting (TEG)., Methods: Standardized full thickness 5cm by 5cm burns were created on each of the backs and flanks of 10 anesthetized female pigs (25kg) using a validated model. The burns were created with a heating device that emits heat at a temperature of 400°C for a period of 30s. The burns were randomized to one of six treatments: no TEG or PRP, no TEG+PRP, early (day 2) TEG and no PRP, early TEG+PRP, late (day 14) TEG and no PRP, and late TEG+PRP. Tangential excision was performed down to viable tissue and autografts were 0.2mm thick. When used, a thin layer of autologous PRP was applied below the graft. All wounds were then treated with a topical antibiotic ointment 3 times weekly for 42 days. Digital images and full thickness biopsies were taken at 9, 11, 14, 18, 21, 28, 35 and 42days after injury to determine percentage reepithelialization, scar depth, and scar contraction. Tissue sections were stained with H&E and viewed by a dermatopathologist masked to treatment assignment., Results: There was no reduction in platelet and white blood cell concentrations in PRP and blood samples for the first 14days after-full thickness burns. A total of 120 burns were created on 10 animals evenly distributed between the six treatment groups. Burns undergoing early TEG reepithelialized fastest and with the thinnest scars followed by late TEG. Burns that did not undergo TEG had the slowest reepithelialization and greatest amount of scarring. Application of PRP had no additional effects on reepithelialization, scar depth, or scar contraction in any of the treatment groups., Conclusions: Addition of PRP had similar effects on reepithelialization and scarring of full thickness porcine burns as standard topical antibiotic ointment regardless of whether the burns underwent excision or grafting or the timing of excision and grafting., (Copyright © 2018 Elsevier Ltd and ISBI. All rights reserved.)

Background: Susceptibility to pepsin digestion of candidate transgene products is regarded an important parameter in the weight-of-evidence approach for allergenicity risk assessment of genetically modified crops. It has been argued that protocols used for this assessment should better reflect physiological conditions encountered in representative food consumption scenarios., Aim: To evaluate whether inclusion of more physiological conditions, such as sub-optimal and lower pepsin concentrations, in combination with pancreatin digestion, improved the performance of digestibility protocols used in characterization of protein stability., Methods: Four pairs of established allergens and their related non/weakly-allergenic counterparts (seed albumins, muscle tropomyosins, plant lipid transfer proteins [LTP] and collagens) plus fish parvalbumin, were subjected to nine combinations of pH (1.2-2.5-4.0) and pepsin-to-protein ratio (PPR: 10-1-0.1 U/µg) for pepsin digestion, followed by pancreatin digestion in the presence of bile salts. Digestion was monitored by SDS-PAGE in conjunction with Coomassie staining and immunoblotting using rabbit antisera and human IgE., Results: At pH 4.0 and at PPR 0.1 most proteins, both allergen and non-allergen, were highly resistant to pepsin. Under conditions known to favor pepsin proteolysis, the established major allergens Ara h 2, Pru p 3 and Pen a 1 were highly resistant to proteolysis, while the allergen Cyp c 1 was not. However, this resistance to pepsin digestion only made Ara h 2 and to a lesser extent Pen a 1 and Pru p 3 stand out compared to their non-allergenic counterparts. Largely irrespective of preceding pepsin digestion conditions, pancreatin digestion was very effective for all tested proteins, allergens and non-allergens, except for Cyp c 1 and bovine collagen., Conclusions: Sub-optimal pH, low pepsin-to protein ratio, and sequential pepsin and pancreatin digestion protocols do not improve the predictive value in distinguish allergens from non-allergens. Digestion conditions facilitating such distinction differ per protein pair.

Soybean ( Glycine max ) is an important food stock, and also considered an allergenic food with at least eight well characterized allergens. However, it is a less prevalent allergen source than many other foods and is rarely life-threatening. Soybean is incorporated into commonly consumed foods, and therefore, the allergens pose a potential concern for individuals already sensitized. The protein profile of soybean can be affected by several factors including genetic and environmental. To investigate how soybean allergen content may be affected by genetics and/or environment, nine soy allergens were quantified from three commercial soybean varieties grown at nine locations in three states within a single climate zone in North America; Iowa, Illinois, and Indiana, United States. Quantitation was achieved using liquid chromatography-selected reaction monitoring (LC-SRM) tandem mass spectrometry with AQUA peptide standards specific to the nine target allergens. Quantitation of allergen concentration indicated that both genetics and location affected specific allergen content. Seven of the nine allergens were significantly influenced by genetics, with the exceptions of glycinin G4 and KTI 3. The allergens P34, Gly m Bd 28k, glycinin G3, and KTI 1 showed statistically significant impact from location as well, but at a lower threshold of significance compared with genetics (cultivar/variety). This dataset contributes to our understanding of the natural variation of endogenous allergens, as it represents a sampling of soybeans grown in a controlled, distributed plot design under agronomic conditions common for commercial soybean food and feed production. The aim was to build upon our recent understanding of how allergens are expressed as part of the overall soybean proteome.

Background Military personnel post-deployment to Iraq and Afghanistan have noted new-onset respiratory illness. This study's primary objective was to further develop an animal model of Iraq Afghanistan War Lung Injury (IAW-LI) and to test a novel class of anti-injury drug called RuX. Methods Particulate Matter (PM) samples were obtained in Iraq then characterized by spectromicroscopy. C57BL/6 mice underwent orotracheal instillation with PM, followed by drinkable treatment with RuX. Lung histology, inspiratory capacity (FlexiVent), thymic/splenic regulatory T cell (Treg) number, and whole-lung genomics were analyzed. Results Tracheal instillation of Iraq PM led to lung septate thickening and lymphocytic inflammation. PM-exposed mice had suppression of thymic/splenic regulatory T-cells (Tregs). Drinking RuX after PM exposure attenuated the histologic lung injury response, improved lung inspiratory capacity, and increased Tregs. Pooled whole lung genomics suggest differences among gene expression of IL-15 among control, PM, and PM + RuX groups. Conclusions RuX, a ruthenium and alpha-lipoic acid complex, attenuates lung injury by improving histology and inspiratory capacity via upregulation of Tregs in Iraq PM-exposed C57BL/6. Plausible genomic effects may involve IL-15 whole lung gene expression.

Protein allergens can be related by cross-reactivity. Allergens that share relevant sequence can cross-react, those lacking sufficient similarity in their IgE antibody-binding epitopes do not cross-react. Cross-reactivity is based on shared epitopes that is based on shared sequence and higher level structure (charge and shape). Epitopes are important in predicting cross-reactivity potential and may provide the potential to establish criteria that identify homology among allergens. Selected allergen's IgE-binding epitope sequences were used to determine how the FASTA algorithm could be used to identify a threshold of significance. A statistical measure (expectation value, E-value) was used to identify a threshold specific to identifying cross-reactivity potential. Peanut Ara h 1 and Ara h 2, shrimp tropomyosin Pen a 1, and birch tree pollen allergen, Bet v 1 were sources of known epitopes. Each epitope or set of epitopes was inserted into random amino acid sequence to create hypothetical proteins used as queries to an allergen database. Alignments with allergens were noted for the ability to match the epitope's source allergen as well as any cross-reactive or other homologous allergens. A FASTA expectation value range (1 × 10 -5 -1 × 10 -6 ) was identified that could act as a threshold to help identify cross-reactivity potential., (© 2017 Syngenta Crop Protection, LLC. Molecular Nutrition & Food Research published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objectives: Research has identified academic disidentification as a phenomenon that appears to uniquely impact Black male students. However, few empirical studies examine what underlies such gender differences. This study examined whether students' teacher trust is a factor underlying academic disidentification in Black college students and whether this is moderated by gender. Academic disidentification was investigated by examining the strength of the relation between a student's view of his or her academic abilities in comparison to peers (i.e., academic self-concept [ASC]) and the student's academic outcomes (i.e., grade point average [GPA]). Attribution theory was used as a lens to test a hypothesized multigroup path model that linked age to teacher trust and ASC, and ASC to GPA through teacher trust. Alternative models were also tested., Method: Participants were 319 Black students (120 males and 199 females) recruited from a large, southwestern, predominantly White university., Results: Results revealed the hypothesized model fit the data reasonably well, whereas the alternative models resulted in a poorer fit. The final model supported our hypothesis that the relation between ASC and GPA is partially mediated by teacher trust and this relation was moderated by gender, such that the indirect effect was significantly stronger for males than females. Several significant differences were also found across gender for direct paths., Conclusions: These findings suggest college students' trust of faculty may be particularly important for Black males and is likely a contributing factor to academic disidentification. Practical implications for university professionals' facilitation of Black college students' academic development are discussed. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

It is known in humans and mouse models, that drinking water exposures to arsenite (As +3 ) leads to immunotoxicity. Previously, our group showed that certain types of immune cells are extremely sensitive to arsenic induced genotoxicity. In order to see if cells from different immune organs have differential sensitivities to As +3 , and if the sensitivities correlate with the intracellular concentrations of arsenic species, male C57BL/6J mice were dosed with 0, 100 and 500ppb As +3 via drinking water for 30d. Oxidation State Specific Hydride Generation- Cryotrapping- Inductively Coupled Plasma- Mass Spectrometry (HG- CT- ICP- MS) was applied to analyze the intracellular arsenic species and concentrations in bone marrow, spleen and thymus cells isolated from the exposed mice. A dose-dependent increase in intracellular monomethylarsonous acid (MMA +3 ) was observed in both bone marrow and thymus cells, but not spleen cells. The total arsenic and MMA +3 levels were correlated with an increase in DNA damage in bone marrow and thymus cells. An in vitro treatment of 5, 50 and 500nM As +3 and MMA +3 revealed that bone marrow cells are most sensitive to As +3 treatment, and MMA +3 is more genotoxic than As +3 . These results suggest that the differential sensitivities of the three immune organs to As +3 exposure are due to the different intracellular arsenic species and concentrations, and that MMA +3 may play a critical role in immunotoxicity., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

In rice, several allergens have been identified such as the non-specific lipid transfer protein-1, the α-amylase/trypsin-inhibitors, the α-globulin, the 33 kDa glyoxalase I (Gly I), the 52-63 kDa globulin, and the granule-bound starch synthetase. The goal of the present study was to define optimal rice extraction and detection methods that would allow a sensitive and reproducible measure of several classes of known rice allergens. In a three-laboratory ring-trial experiment, several protein extraction methods were first compared and analyzed by 1D multiplexed SDS-PAGE. In a second phase, an inter-laboratory validation of 2D-DIGE analysis was conducted in five independent laboratories, focusing on three rice allergens (52 kDa globulin, 33 kDa glyoxalase I, and 14-16 kDa α-amylase/trypsin inhibitor family members). The results of the present study indicate that a combination of 1D multiplexed SDS-PAGE and 2D-DIGE methods would be recommended to quantify the various rice allergens.

Genetically modified (GM) crops have achieved success in the marketplace and their benefits extend beyond the overall increase in harvest yields to include lowered use of insecticides and decreased carbon dioxide emissions. The most widely grown GM crops contain gene/s for targeted insect protection, herbicide tolerance, or both. Plant expression of Bacillus thuringiensis (Bt) crystal (Cry) insecticidal proteins have been the primary way to impart insect resistance in GM crops. Although deemed safe by regulatory agencies globally, previous studies have been the basis for discussions around the potential immuno-adjuvant effects of Cry proteins. These studies had limitations in study design. The studies used animal models with extremely high doses of Cry proteins, which when given using the ig route were co-administered with an adjuvant. Although the presumption exists that Cry proteins may have immunostimulatory activity and therefore an adjuvanticity risk, the evidence shows that Cry proteins are expressed at very low levels in GM crops and are unlikely to function as adjuvants. This conclusion is based on critical review of the published literature on the effects of immunomodulation by Cry proteins, the history of safe use of Cry proteins in foods, safety of the Bt donor organisms, and pre-market weight-of-evidence-based safety assessments for GM crops., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Current evidence supports the use of excision to remove eschar from deep dermal and full-thickness burns. However, the role of excision of mid-dermal burns remains unclear. This study aimed to develop a porcine model that could produce reproducible middermal thermal burns that undergo tangential excision; and investigate the effects of immediate tangential excision (30 minutes postburn) on healing and scarring. An aluminum bar preheated in hot water (70°C) was applied for 20 or 30 s to produce a total of sixteen mid-dermal burns per pig on each of six pigs. Thirty minutes after burn creation, half of the burns were tangentially excised. Four partial- thickness wounds per pig were created as controls. Depth of burn injury (1 and 24 h), reepithelialization (7 and 10 d) and scar depth (28 d) were assessed microscopically. Total scar surface area was grossly evaluated on day 28. Exposure of porcine skin to a preheated aluminum bar at 70 °C for 20 or 30 sec resulted in reproducible mid-dermal burns, where immediate excision enhanced complete wound closure as judged by complete re-epithelialization, but did not reduce initial depth of injury, scar contraction and scar depth. Immediate surgical intervention is sufficient to enhance wound closure, but not to mitigate mid-dermal burn scar formation. This work provides a suitable animal model to evaluate novel therapies that may be used to inhibit burn progression, accelerate wound closure and decrease scarring, especially those therapies unable to penetrate burn eschar.

Introduction: Current methods of assessing burn depth are limited and are primarily based on visual assessments by burn surgeons. This technique has been shown to have only 60% accuracy and a more accurate, simple, noninvasive method is needed to determine burn wound depth. Forward-looking infrared (FLIR) thermography is both noninvasive and user-friendly with the potential to rapidly assess burn depth. The purpose of this paper is to determine if early changes in burn temperature (first 3 days) can be a predictor of burn depth as assessed by vertical scarring 28 days after injury., Methods: While under general anesthesia, 20 burns were created on the backs of two female Yorkshire swine using a 2.5cm×2.5cm×7.5cm, 150g aluminum bar, for a total of 40 burns. FLIR imaging was performed at both early (1, 2 and 3 days) and late (7, 10, 14, 17, 21, 24 and 28 days) time points. Burns were imaged from a height of 12 inches from the skin surface. FLIR ExaminIR(©) software was used to examine the infrared thermographs. One hundred temperature points from burn edge to edge across the center of the burn were collected for each burn at all time points and were exported as a comma-separated values (CSV) file. The CSV file was processed and analyzed using a MATLAB program. The temperature profiles through the center of the burns generated parabola-like curves. The lowest temperature (temperature minimum) and a line midway between the temperature minimum and ambient skin temperature at the burn edges was defined and the area of the curve calculated (the "temperature half-area")., Results: Half-area values 2 days after burn had higher correlations with scar depth than did the minimum temperatures. However, burns that became warmer from 1 day to 2 days after injury had a lower scar depth then burns that became cooler and this trend was best predicted by temperature minima. When data were analyzed as a diagnostic test for sensitivity and specificity using >3mm scarring, i.e. a full-thickness burn, as a clinically relevant criterion standard, temperature minima at 2 days after burn was found to be the most sensitive and specific test., Conclusions: FLIR imaging is a fast and simple tool that has been shown to predict burn wound outcome in a porcine vertical injury progression model. Data showed that more severe burn wounds get cooler between 1 and 2 days after burn. We found four analytic methods of FLIR images that were predictive of burn progression at 1 and 2 days after burn; however, temperature minima 2 days after burn appeared to be the best predictive test for injury progression to a full-thickness burn. Although these results must be validated in clinical studies, FLIR imaging has the potential to aid clinicians in assessing burn severity and thereby assisting in burn wound management., (Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.)

Introduction: In order to be useful, animal models should be reproducible and consistent regardless of sampling bias, investigator creating burn, and burn location. We determined the variability in burn depth based on biopsy location, burn location and investigator in a porcine model of partial thickness burns., Methods: 24 partial thickness burns (2.5 cm by 2.5 cm each) were created on the backs of 2 anesthetized pigs by 2 investigators (one experienced, one inexperienced) using a previously validated model. In one of the pigs, the necrotic epidermis covering each burn was removed. Five full thickness 4mm punch biopsies were obtained 1h after injury from the four corners and center of the burns and stained with Hematoxylin and Eosin and Masson's trichrome for determination of burn depth by a board certified dermatopathologist blinded to burn location and investigator. Comparisons of burn depth by biopsy location, burn location and investigator were performed with t-tests and ANOVA as appropriate., Results: The mean (SD) depth of injury to blood vessels (the main determinant of burn progression) in debrided and non-debrided pigs pooled together was 1.8 (0.3)mm, which included 75% of the dermal depth. Non-debrided burns were 0.24 mm deeper than debrided burns (P<0.001). Burn depth increased marginally from cephalic to caudal in non-debrided burns, but showed no statistical differences for these locations, in debrided burns. Additionally, there were also no statistical differences in burn depths from midline to lateral in either of these burn types. Burn depth was similar for both investigators and among biopsy locations., Conclusions: Burn depth was greater for caudal locations in non-debrided burns and overall non-debrided burns were deeper than debrided burns. However, burn depth did not differ based on investigator, biopsy site, and medial-lateral location., (Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.)

Previous studies have shown that complex mixtures containing particulate matter (PM) and polycyclic aromatic hydrocarbons (PAHs) produce systemic immunotoxicity in animal models following inhalation exposures. While we and others have shown that emissions associated with hardwood smoke (HWS), cigarette smoke and diesel exhaust can suppress the immune systems of animals in vitro and in vivo, there have been few immune function studies on human peripheral blood mononuclear cells (HPBMC) following exposure of humans to HWS. Our work shows that T cells are an important targets of PM and PAH immunotoxicity. These studies were conducted on HPBMC from 14 human volunteers receiving four 2 h nightly exposures to clean air or HWS at a concentration of 500 ug/m(3). We measured anti-CD3/anti-CD28 stimulated T-cell proliferation and HPBMC cytokine production in cell supernatants, including interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), interleukin 8 (IL-8), TH1 cytokines γIFN and IL-2, TH2 cytokine IL-4, Th17 cytokine interleukin 17A (IL-17A) and interleukin 10 (IL-10). We analyzed results using analysis of variance (ANOVA), t-tests and Pearson correlation. Results showed that there was significant variation in the amount of T-cell proliferation observed following polyclonal activation with anti-CD3/anti-CD28 antibodies in both the air and HWS-exposed groups. There was not a significant effect of HWS on T-cell proliferation. However, we did find a strong relationship between the presence of proinflammatory cytokines (IL-1β, TNF-α, IL-6, but not IL-8) and the amount of T-cell proliferation seen in individual donors, demonstrating that brief exposures of humans to HWS can produce changes in systemic immunity that is associated with proinflammatory cytokines.

The current study examined body image concerns among African American women. In recent years, there has been an attempt to include ethnic minority samples in body image studies (e.g., Grabe & Hyde, 2006; Hrabosky & Grilo, 2007; Lovejoy, 2001) but few specifically examine unique issues pertaining to beauty and body image for African American college age women. A total of 31 African American women participated in one of five focus groups on the campus of a large Southwestern University to examine beauty and body image. Data were analyzed using a thematic approach and several themes were identified. The majority of themes pertained to issues related to hair, skin tone, body type, and message sources. Themes included: sacrifice, ignorance/racial microaggressions, and validation and invalidation by others, thick/toned/curvy as optimal, hypersexualization, and being thin is for White women. Findings of the current study suggest a reconceptualization of body image for African American women where relevant characteristics such as hair and skin tone are given more priority over traditional body image concerns often associated with European American women.