Glutenin from the Ancient Wheat Progenitor Is Intrinsically Allergenic as It Can Clinically Sensitize Mice for Systemic Anaphylaxis by Activating Th2 Immune Pathway.

Wheat allergy is a major type of food allergy with the potential for life-threatening anaphylactic reactions. Common wheat, Triticum aestivum (hexaploid, AABBDD genome), was developed using tetraploid wheat (AABB genome) and the ancient diploid wheat progenitor (DD genome)-Aegilops tauschii. The potential allergenicity of gluten from ancient diploid wheat is unknown. In this study, using a novel adjuvant-free gluten allergy mouse model, we tested the hypothesis that the glutenin extract from this ancient wheat progenitor will be intrinsically allergenic in this model. The ancient wheat was grown, and wheat berries were used to extract the glutenin for testing. A plant protein-free colony of Balb/c mice was established and used in this study. The intrinsic allergic sensitization potential of the glutenin was determined by measuring IgE response upon transdermal exposure without the use of an adjuvant. Clinical sensitization for eliciting systemic anaphylaxis (SA) was determined by quantifying the hypothermic shock response (HSR) and the mucosal mast cell response (MMCR) upon intraperitoneal injection. Glutenin extract elicited a robust and specific IgE response. Life-threatening SA associated and a significant MMCR were induced by the glutenin challenge. Furthermore, proteomic analysis of the spleen tissue revealed evidence of in vivo Th2 pathway activation. In addition, using a recently published fold-change analysis method, several immune markers positively and negatively associated with SA were identified. These results demonstrate for the first time that the glutenin from the ancient wheat progenitor is intrinsically allergenic, as it has the capacity to elicit clinical sensitization for anaphylaxis via activation of the Th2 pathway in vivo in mice.

Advances in Gluten Hypersensitivity: Novel Dietary-Based Therapeutics in Research and Development.

Gluten hypersensitivity is characterized by the production of IgE antibodies against specific wheat proteins (allergens) and a myriad of clinical allergic symptoms including life-threatening anaphylaxis. Currently, the only recommended treatment for gluten hypersensitivity is the complete avoidance of gluten. There have been extensive efforts to develop dietary-based novel therapeutics for combating this disorder. There were four objectives for this study: (i) to compile the current understanding of the mechanism of gluten hypersensitivity; (ii) to critically evaluate the outcome from preclinical testing of novel therapeutics in animal models; (iii) to determine the potential of novel dietary-based therapeutic approaches under development in humans; and (iv) to synthesize the outcomes from these studies and identify the gaps in research to inform future translational research. We used Google Scholar and PubMed databases with appropriate keywords to retrieve published papers. All material was thoroughly checked to obtain the relevant data to address the objectives. Our findings collectively demonstrate that there are at least five promising dietary-based therapeutic approaches for mitigating gluten hypersensitivity in development. Of these, two have advanced to a limited human clinical trial, and the others are at the preclinical testing level. Further translational research is expected to offer novel dietary-based therapeutic options for patients with gluten hypersensitivity in the future.

Risk factors for Salmonella Dublin on dairy farms in Ontario, Canada.

Salmonella Dublin is an emerging pathogen on dairy farms in Canada. In Ontario, Salmonella Dublin has been increasingly isolated from diagnostic laboratory samples. The objective of this observational cross-sectional study was to identify management practices associated with herd positivity for Salmonella Dublin. A convenience sample of 100 dairy farms was visited in Ontario, Canada, from April to August 2022. Farms were visited once to collect blood samples from 20 heifers between 4 and 24 mo old, sample bulk tank milk, and administer an in-person questionnaire on management practices. An additional bulk tank milk sample was collected before the visit by milk transporters. All bulk tank and serum samples underwent ELISA testing to determine Salmonella Dublin positivity (≥35% positivity on ELISA). Of the 1,990 heifers sampled, 44 (2.2%) animals were seropositive for Salmonella Dublin. At least one seropositive heifer was identified on 24% of participating farms. Based on the bulk tank milk samples collected during both sampling periods, 4% of farms were positive for Salmonella Dublin. Overall, of the 100 farms visited, 25% were classified as Salmonella Dublin positive, meaning at least one serum or bulk tank sample was interpreted as positive. A multivariable logistic regression model identified 5 factors associated with herd-level positivity for Salmonella Dublin. Specifically, introducing purchased animals within the last 2 years increased the likelihood that farms were positive for Salmonella Dublin (odds ratio [OR] = 4.6). Farms that had at least one animal leave the premises for a cattle show, embryo collection center, or loan to another farm and return within the last 2 years were also at a higher risk for Salmonella Dublin (OR = 4.9). Farms that removed manure from the surface of bedding in calving pens twice per month or after every calving were at greater risk for Salmonella Dublin than farms that removed manure less frequently (OR = 8.5). Farms that added bedding material to calving areas once or twice weekly were at lower risk for Salmonella Dublin compared with farms that added bedding less than once weekly (OR = 0.1). In addition, farms that kept 3 cows or less per pen in the calving area were at lower risk for Salmonella Dublin. Test positivity for Salmonella Dublin among Ontario dairy farms sampled is high, and dairy producers should consider avoiding management practices that are associated with an increased risk of Salmonella Dublin infection.

Intrinsic Allergenicity Potential of Salt-Soluble Protein Extracts from the Diploid, Tetraploid and Hexaploid Wheats: Validation Using an Adjuvant-Free Mouse Model.

Wheat allergies are potentially life-threatening and, therefore, have become a major health concern at the global level. It is largely unknown at present whether genetic variation in allergenicity potential exists among hexaploid, tetraploid and diploid wheat species. Such information is critical in establishing a baseline allergenicity map to inform breeding efforts to identify hyper-, hypo- and non-allergenic varieties. We recently reported a novel mouse model of intrinsic allergenicity using the salt-soluble protein extract (SSPE) from durum, a tetraploid wheat (Triticum durum). Here, we validated the model for three other wheat species [hexaploid common wheat (Triticum aestivum), diploid einkorn wheat (Triticum monococcum), and the ancient diploid wheat progenitor, Aegilops tauschii], and then tested the hypothesis that the SSPEs from wheat species will exhibit differences in relative allergenicities. Balb/c mice were repeatedly exposed to SSPEs via the skin. Allergic sensitization potential was assessed by specific (s) IgE antibody responses. Oral anaphylaxis was quantified by the hypothermic shock response (HSR). The mucosal mast cell response (MMCR) was determined by measuring mast cell protease in the blood. While T. monococcum elicited the least, but significant, sensitization, others were comparable. Whereas Ae. taushcii elicited the least HSR, the other three elicited much higher HSRs. Similarly, while Ae. tauschii elicited the least MMCR, the other wheats elicited much higher MMCR as well. In conclusion, this pre-clinical comparative mapping strategy may be used to identify potentially hyper-, hypo- and non-allergenic wheat varieties via crossbreeding and genetic engineering methods.

Is Wheat Glutenin Extract Intrinsically Allergenic? Evaluation Using a Novel Adjuvant-Free Mouse Model of Systemic Anaphylaxis.

Wheat is a prominent allergenic food that can trigger life-threatening anaphylaxis. Presently, it remains unclear whether wheat glutenin (WG) extract possesses inherent sensitization potential independently, without the use of adjuvants, and whether it can sensitize mice to the extent of inducing life-threatening systemic anaphylaxis. In this study, we tested the hypothesis that repeated skin exposures to WG extract without adjuvant will sensitize mice with the resultant anaphylactic reaction upon systemic WG challenge. Balb/c mice were bred and maintained on a strict plant protein-free diet and were repeatedly exposed to a WG extract or vehicle once a week for 9 weeks. WG-specific (s)IgE and total (t)IgE levels were quantified. Mice were challenged with WG extract to induce anaphylactic reactions as measured by hypothermic shock response (HSR) and mucosal mast cell degranulation response (MMCR). We also conducted proteomic analysis of 120 spleen immune markers. These skin-sensitized mice exhibited exposure-dependent IgE responses and near-fatal anaphylaxis upon challenge. Proteomic analysis identified seven dramatically elevated immune biomarkers in anaphylactic mice. These data reveal that WG is intrinsically allergenic, and that chronic skin exposure to WG extract can prime the mice for potentially fatal anaphylaxis.

A Mouse-Based Method to Monitor Wheat Allergens in Novel Wheat Lines and Varieties Created by Crossbreeding: Proof-of-Concept Using Durum and A. tauschii Wheats.

Wheat allergies are potentially life-threatening because of the high risk of anaphylaxis. Wheats belong to four genotypes represented in thousands of lines and varieties. Monitoring changes to wheat allergens is critical to prevent inadvertent ntroduction of hyper-allergenic varieties via breeding. However, validated methods for this purpose are unavailable at present. As a proof-of-concept study, we tested the hypothesis that salt-soluble wheat allergens in our mouse model will be identical to those reported for humans. Groups of Balb/cJ mice were rendered allergic to durum wheat salt-soluble protein extract (SSPE). Using blood from allergic mice, a mini hyper-IgE plasma bank was created and used in optimizing an IgE Western blotting (IEWB) to identify IgE binding allergens. The LC-MS/MS was used to sequence the allergenic bands. An ancient Aegilops tauschii wheat was grown in our greenhouse and extracted SSPE. Using the optimized IEWB method followed by sequencing, the cross-reacting allergens in A. tauschii wheat were identified. Database analysis showed all but 2 of the durum wheat allergens and all A. tauschii wheat allergens identified in this model had been reported as human allergens. Thus, this model may be used to identify and monitor potential changes to salt-soluble wheat allergens caused by breeding.

Prospective Assessment of SARS-CoV-2 Seroconversion (PASS) study: an observational cohort study of SARS-CoV-2 infection and vaccination in healthcare workers.

BACKGROUND: SARS-CoV-2 is a recently emerged pandemic coronavirus (CoV) capable of causing severe respiratory illness. However, a significant number of infected people present as asymptomatic or pauci-symptomatic. In this prospective assessment of at-risk healthcare workers (HCWs) we seek to determine whether pre-existing antibody or T cell responses to previous seasonal human coronavirus (HCoV) infections affect immunological or clinical responses to SARS-CoV-2 infection or vaccination. METHODS: A cohort of 300 healthcare workers, confirmed negative for SARS-CoV-2 exposure upon study entry, will be followed for up to 1 year with monthly serology analysis of IgM and IgG antibodies against the spike proteins of SARS-CoV-2 and the four major seasonal human coronavirus - HCoV-OC43, HCoV-HKU1, HCoV-229E, and HCoV-NL63. Participants will complete monthly questionnaires that ask about Coronavirus Disease 2019 (COVID-19) exposure risks, and a standardized, validated symptom questionnaire (scoring viral respiratory disease symptoms, intensity and severity) at least twice monthly and any day when any symptoms manifest. SARS-CoV-2 PCR testing will be performed any time participants develop symptoms consistent with COVID-19. For those individuals that seroconvert and/or test positive by SARS-CoV-2 PCR, or receive the SARS-CoV-2 vaccine, additional studies of T cell activation and cytokine production in response to SARS-CoV-2 peptide pools and analysis of Natural Killer cell numbers and function will be conducted on that participant's cryopreserved baseline peripheral blood mononuclear cells (PBMCs). Following the first year of this study we will further analyze those participants having tested positive for COVID-19, and/or having received an authorized/licensed SARS-CoV-2 vaccine, quarterly (year 2) and semi-annually (years 3 and 4) to investigate immune response longevity. DISCUSSION: This study will determine the frequency of asymptomatic and pauci-symptomatic SARS-CoV-2 infection in a cohort of at-risk healthcare workers. Baseline and longitudinal assays will determine the frequency and magnitude of anti-spike glycoprotein antibodies to the seasonal HCoV-OC43, HCoV-HKU1, HCoV-229E, and HCoV-NL63, and may inform whether pre-existing antibodies to these human coronaviruses are associated with altered COVID-19 disease course. Finally, this study will evaluate whether pre-existing immune responses to seasonal HCoVs affect the magnitude and duration of antibody and T cell responses to SARS-CoV-2 vaccination, adjusting for demographic covariates.

Creating hypo-/nonallergenic wheat products using processing methods: Fact or fiction?

Wheat allergy is a potentiallylife-threatening disease that affects millions of people around the world. Food processing has been shown to influence the allergenicity of wheat and other major foods. However, a comprehensive review evaluating whether or not food processing can be used to develop hypo-/nonallergenic wheat products is unavailable. There were three objectives for this study: (1) to critically evaluate the evidence on the effect of fermentation, thermal processing, and enzyme or acid hydrolysis on wheat allergenicity so as to identify the potential for and challenges of using these methods to produce hypo-/nonallergenic wheat products; (2) to identify the molecular effects of food processing needed to create such products; and (3) to map the concept questions for future research and development to produce hypo-/nonallergenic wheat products. We performed literature research using PubMed and Google Scholar databases with various combinations of keywords to generate the data to accomplish these objectives. We found that: (1) food processing significantly modulates wheat allergenicity; while some methods can reduce or even abolish the allergenicity, others can create mega allergens; and (2) fermentation and enzymatic hydrolysis hold the most potential to create novel hypo-/nonallergenic wheat products; however, preclinical validation and human clinical trials are currently lacking. We also identify five specific research concepts to advance the research to enable the creation of hypo-/nonallergenic wheat products for application in food, medical, and cosmetic industries.

Mechanisms of Wheat Allergenicity in Mice: Comparison of Adjuvant-Free vs. Alum-Adjuvant Models.

Wheat protein is considered a major type of food allergen in many countries including the USA. The mechanisms of allergenicity of wheat proteins are not well understood at present. Both adjuvant-based and adjuvant-free mouse models are reported for this food allergy. However, it is unclear whether the mechanisms underlying wheat allergenicity in these two types of models are similar or different. Therefore, we compared the molecular mechanisms in a novel adjuvant-free (AF) model vs. a conventional alum-adjuvant (AA) model of wheat allergy using salt-soluble wheat protein (SSWP). In the AF model, Balb/cJ mice were sensitized with SSWP via skin exposure. In the AA model, mice were sensitized by an intraperitoneal injection of SSWP with alum. In both models, allergic reactions were elicited using an identical protocol. Robust IgE as well as mucosal mast cell protein-1 responses were elicited similarly in both models. However, an analysis of the spleen immune markers identified strikingly different molecular activation patterns in these two models. Furthermore, a number of immune markers associated with intrinsic allergenicity were also identified in both models. Since the AF model uses skin exposure without an adjuvant, the mechanisms in the AF model may more closely simulate the human wheat allergenicity mechanisms from skin exposure in occupational settings such as in the baking industry.

Genomic Analysis of Cardiac Surgery-Associated Mycobacterium chimaera Infections, United States.

A surgical heater-cooler unit has been implicated as the source for Mycobacterium chimaera infections among cardiac surgery patients in several countries. We isolated M. chimaera from heater-cooler units and patient infections in the United States. Whole-genome sequencing corroborated a risk for these units acting as a reservoir for this pathogen.

Conjugal Transfer, Whole-Genome Sequencing, and Plasmid Analysis of Four mcr-1-Bearing Isolates from U.S. Patients.

Four Enterobacteriaceae clinical isolates bearing mcr-1 gene-harboring plasmids were characterized. All isolates demonstrated the ability to transfer colistin resistance to Escherichia coli; plasmids were stable in conjugants after multiple passages on nonselective media. mcr-1 was located on an IncX4 (n = 3) or IncN (n = 1) plasmid. The IncN plasmid harbored 13 additional antimicrobial resistance genes. Results indicate that the mcr-1-bearing plasmids in this study were highly transferable in vitro and stable in the recipients.

Improved Antibody Response to Three Additional Hepatitis B Vaccine Doses Following Primary Vaccination Failure in Patients with Inflammatory Bowel Disease.

BACKGROUND: Studies have shown the efficacy of hepatitis B (HBV) vaccination in patients with inflammatory bowel disease (IBD) is impaired, but few data exist regarding the effectiveness of revaccination strategies following primary vaccination failure. Our aim was to analyze the association between administration of additional vaccine doses and hepatitis B surface antibody (HBsAb) seroconversion. METHODS: This is a retrospective cohort study. Inclusion criteria are as follows: age ≥ 18, diagnosis of Crohn's disease (CD) or ulcerative colitis (UC), inadequate HBsAb < 10 IU/L following initial HBV vaccination series, subsequent administration of 1-3 additional doses of HBV vaccine with follow-up serum HBsAb measurements. Patients were stratified into groups of ≤ 2 or 3 doses received. Primary outcome was achieving HBsAb > 10 IU/L. Outcomes were stratified by age ≥ or < 40 years. We performed logistic and linear multivariable regression analyses for categorical and continuous data. RESULTS: The study cohort consists of (n = 149) 54.4% women; 77.9% white; 72.6% with CD, with mean age: 46.2. Patients of all ages and age ≥ 40 years, who received 3 additional doses of vaccine, were more likely to achieve seroprotective HBsAb levels than patients who received 1 or 2 doses (OR 1.77, P = 0.01; OR 1.9, P = 0.03, respectively, after adjusting for age, sex, race, immunosuppressive medication exposure, time between vaccine/titer). CONCLUSIONS: Following initial HBV vaccination failure, patients with IBD of all ages are more likely to develop seroprotective levels of HBsAb following 3 additional vaccine doses, rather than 1 or 2 alone. In patients who fail primary HBV vaccination, providers should consider a more aggressive revaccination strategy with an additional 3-dose series.

Advances in Molecular Mechanisms of Wheat Allergenicity in Animal Models: A Comprehensive Review.

The prevalence of wheat allergy has reached significant levels in many countries. Therefore, wheat is a major global food safety and public health issue. Animal models serve as critical tools to advance the understanding of the mechanisms of wheat allergenicity to develop preventive and control methods. A comprehensive review on the molecular mechanisms of wheat allergenicity using animal models is unavailable at present. There were two major objectives of this study: To identify the lessons that animal models have taught us regarding the molecular mechanisms of wheat allergenicity and to identify the strengths, challenges, and future prospects of animal models in basic and applied wheat allergy research. Using the PubMed and Google Scholar databases, we retrieved and critically analyzed the relevant articles and excluded celiac disease and non-celiac gluten sensitivity. Our analysis shows that animal models can provide insight into the IgE epitope structure of wheat allergens, effects of detergents and other chemicals on wheat allergenicity, and the role of genetics, microbiome, and food processing in wheat allergy. Although animal models have inherent limitations, they are critical to advance knowledge on the molecular mechanisms of wheat allergenicity. They can also serve as highly useful pre-clinical testing tools to develop safer genetically modified wheat, hypoallergenic wheat products, novel pharmaceuticals, and vaccines.

Accessing support before or after a parent dies from cancer and young people's current wellbeing.

PURPOSE: To examine differences in distress and unmet needs between bereaved adolescent and young adult (AYA) offspring who accessed support before and after being bereaved by parental cancer, and to explore aspects of their cancer experience that influenced their help-seeking. METHODS: Phase 1: Surveys completed by AYAs (11-26 years) bereaved by parental cancer were subjected to analysis of covariance examining differences in distress and unmet needs between those who accessed support before (n = 159) and after (n = 212) parental bereavement. Phase 2: Semi-structured interviews explored the cancer experiences of bereaved offspring (n = 8) and factors that influenced their decision to seek support. RESULTS: Phase 1: There were no significant group differences in distress and unmet needs; however, older and female AYAs reported higher levels of distress and unmet needs. Interestingly, individuals who accessed support pre-bereavement were older on average (M = 17.35 years, SD = 3.26) than those who accessed support post-bereavement (M = 15.73 years, SD = 3.26). Phase 2: Three themes emerged centred on socio-emotional developmental changes during and after the cancer trajectory. These related to: participants' meaning-making and changes in understanding of the cancer experience, changing relationships and desires to fit in, and understanding of their own emotional needs. CONCLUSIONS: While no differences were found in unmet needs and distress between those who sought support pre- or post-bereavement, those seeking support pre-bereavement were older on average. Social and emotional development impacts how bereaved offspring access psychosocial support. Awareness of these issues can assist in improving support by ensuring services are age appropriate and families are sufficiently supported.

The Pain Course: exploring the feasibility of an internet-delivered pain management programme for adults with spinal cord injury.

STUDY DESIGN: Single-group feasibility clinical trial. OBJECTIVES: This study examined the feasibility and outcomes of a modified version of a validated internet-delivered pain management programme, the Pain Course, for adults with SCI. SETTING: Nationwide in Australia. METHODS: Sixty-eight adults participated in the programme, which comprises five online lessons and homework tasks that are systematically released over 8 weeks. Participants were supported through the course with weekly contact from a clinical psychologist. RESULTS: Eighty-five percent of participants provided data at post-treatment and 76% of participants completed all five lessons of the course. High levels of satisfaction were observed and relatively little clinician time (M = 93.16 min; SD = 52.76 min) was required per participant to provide the course. Preliminary evidence of clinical improvements in pain-related disability (ds ≥ 0.53.; avg. improvement ≥ 20%; Mdiff ≥ 7.77), depression (ds ≥ 0.44.; avg. improvement ≥ 24%; Mdiff ≥ 2.44), anxiety (ds ≥ 0.41.; avg. improvement ≥ 26%; Mdiff ≥ 1.8) and average pain intensity (ds ≥ 0.46.; avg. improvement ≥ 13%; Mdiff ≥ 0.71) were observed at post-treatment, which were maintained or further improved to 3-month follow-up. These improvements were reflected in overall improvements in self-reported satisfaction with life (ds ≥ 0.31; avg. improvement ≥ 25%; Mdiff ≥ 2.16) CONCLUSION: These findings highlight the potential of carefully developed internet-delivered interventions as an approach for overcoming barriers and increasing access to psychosocial care for adults with SCI. SPONSORSHIP: iCare Lifetime Care and Support Authority and the Australian National Health and Medical Research Council.

Adherence to clinic recommendations among patients with phenylketonuria in the United States.

OBJECTIVE: Assess current management practices of phenylketonuria (PKU) clinics across the United States (US) based on the key treatment metrics of blood phenylalanine (Phe) concentrations and blood Phe testing frequency, as well as patient adherence to their clinic's management practice recommendations. METHODS: An online survey was conducted with medical professionals from PKU clinics across the US from July to September 2015. Forty-four clinics participated in the survey and account for approximately half of PKU patients currently followed in clinics in the US (Berry et al., 2013). RESULTS: The majority of PKU clinics recommended target blood Phe concentrations to be between 120 and 360µM for all patients; the upper threshold was relaxed by some clinics for adult patients (from 360 to 600µM) and tightened for patients who are pregnant/planning to become pregnant (to 240µM). Patient adherence to these recommendations (percentage of patients with blood Phe below the upper recommended threshold) was age-dependent, decreasing from 88% in the 0-4years age group to 33% in adults 30+ years. Patient adherence to recommendations for blood testing frequency followed a similar trend. Higher staffing intensity (specialists per 100 PKU patients) was associated with better patient adherence to clinics' blood Phe concentrations recommendations. CONCLUSION: Clinic recommendations of target blood Phe concentrations in the US are now stricter compared to prior years, and largely reflect recent guidelines by the American College of Medical Genetics and Genomics (Vockley et al., 2014). Adherence to recommended Phe concentrations remains suboptimal, especially in older patients. However, despite remaining above the guidelines, actual blood Phe concentrations in adolescents and adults are lower than those reported in the past (Walter et al., 2002; Freehauf et al., 2013). Continued education and support for PKU patients by healthcare professionals, including adequate clinic staffing, are needed to improve adherence. Future research is needed to understand how to improve adherence to reduce the number of patients lost to follow-up, as the findings of this and similar surveys do not address how to keep patients in clinic.

A Mouse Model of Anaphylaxis and Atopic Dermatitis to Salt-Soluble Wheat Protein Extract.

BACKGROUND: Wheat allergy and other immune-mediated disorders triggered by wheat proteins are growing at an alarming rate for reasons not well understood. A mouse model to study hypersensitivity responses to salt-soluble wheat protein (SSWP) extract is currently unavailable. Here we tested the hypothesis that SSWP extract from wheat will induce sensitization as well as allergic disease in mice. METHODS: Female BALB/cJ mice were weaned onto a plant protein-free diet. The mice were injected a total of 4 times with an SSWP (0.01 mg/mouse) fraction extracted from durum wheat along with alum as an adjuvant. Blood was collected biweekly and SSWP-specific IgE (SIgE) and total IgE (TIgE) levels were measured using ELISA. Systemic anaphylaxis upon intraperitoneal injection with SSWP was quantified by hypothermia shock response (HSR). Mucosal mast cell degranulation was measured by the elevation of mMCP-1 in the blood. The mice were monitored for dermatitis. Skin tissues were used in histopathology and for measuring cytokine/chemokine/adhesion molecule levels using a protein microarray system. RESULTS: Injection with SSWP resulted in time-dependent SIgE antibody responses associated with the elevation of TIgE concentration. Challenge with SSWP elicited severe HSR that correlated with a significant elevation of plasma mMCP-1 levels. Sensitized mice developed facial dermatitis associated with mast cell degranulation. Lesions expressed significant elevation of Th2/Th17/Th1 cytokines and chemokines and E-selectin adhesion molecule. CONCLUSION: Here we report a mouse model of anaphylaxis and atopic dermatitis to SSWP extract that may be used for further basic and applied research on wheat allergy.

Omission of preoperative esophageal manometry does not alter operative approach or postoperative dysphagia following laparoscopic paraesophageal hernia repair.

Routine esophageal manometry for surgical planning before laparoscopic paraesophageal hernia (PEH) has been advocated in an effort to reduce the likelihood of postoperative dysphagia. The purpose of this study is to investigate whether omitting routine preoperative esophageal manometry is associated with a change in the type of fundoplication performed and with an increase in the incidence of postoperative dysphagia. A retrospective cohort study of consecutive patients with and without preoperative esophageal manometry undergoing PEH repair was performed between January 2011 and July 2014 at an academic medical center. Demographic and outcome data were collected in a prospective database. The primary outcome measures were the type of fundoplication performed and postoperative disease-specific quality-of-life (GERD-HRQL) dysphagia score. Secondary outcome measures were total GERD-HRQL score, proton pump inhibitor (PPI) use, and requirement for endoscopic dilation. One hundred twenty-five patients underwent laparoscopic PEH repair. Forty-seven (37%) patients had preoperative manometry and 79 (63%) did not. Patients who did not have manometry were older (67.9 ± 14.3 vs. 61.7 ± 13.5, P = 0.02), but the groups did not differ in terms of BMI, gender, PPI use, baseline GERD-HRQL dysphagia score, or baseline total GERD-HRQL score. Sixty-nine (87%) patients without manometry and 43 (93%) patients with manometry underwent a complete fundoplication (P = 0.55). At a median follow-up of 16 (4-44) months, the median GERD-HRQL dysphagia scores (0(0-1) vs. 0(0-1); P = 0.66) and total GERD-HRQL scores (3(1-8) vs. 4(0-8); P = 0.72) were equivalent between the groups. Equivalent proportion of patients without and with preoperative manometry used PPI (9% vs. 21%; P = 0.06) and required endoscopic dilation (6% vs. 6%; P = 0.99) in the postoperative period. Omission of routine preoperative manometry prior to laparoscopic PEH repair is not associated with a change in the type of fundoplication performed, an increased incidence of postoperative dysphagia, or an increased requirement for postoperative endoscopic dilation.

Outcomes of nutritional interventions to treat dysphagia in esophageal cancer: a population-based study.

Esophageal cancer (EC) is increasing in prevalence due to rising incidence and improved treatment strategies. Dysphagia is a significant morbidity in patients with EC requiring nutritional intervention. We sought to evaluate outcomes of nutritional interventions for EC patients hospitalized with dysphagia at a population level. The National Inpatient Sample (2002-2012) was utilized to include all adult inpatients (≥18 years of age) with EC and presence of dysphagia and stricture that underwent nutritional interventions including feeding tube (FT) placement, esophageal stenting, or parenteral nutrition (PN). Temporal trends were examined with multivariate analysis performed for mortality, length of stay (LOS), and cost of hospitalization. A total of 509,593 EC patients had 12,205 hospitalizations related to dysphagia. The hospitalization rates doubled over the study period (1.52% vs. 3.28%, p < 0.001). The most common nutritional intervention was FT (27%), followed by esophageal stenting (13%), and PN (11%). PN was more frequently associated with a diagnosis of sepsis (6.1%, p = 0.023) compared to FT (2.5%) or esophageal stenting (1.8%). Multivariate analysis demonstrated FT and esophageal stenting had comparable mortality (OR 1.06, 95% CI: 0.49, 2.32); however, PN was associated with higher mortality (OR 2.37, 95% CI: 1.22, 4.63), cost of hospitalization ($5,510, 95% CI: 2,262, 8,759), and LOS (2.13 days, 95% CI: 0.72, 3.54). This study shows that hospitalizations for EC with dysphagia and related nutritional interventions are increasing. As a single modality, parenteral nutrition should be avoided. Among our esophageal stent and FT population, further studies are necessary to determine adequate interventions based on disease stage.

Assessment of myocardial metabolic flexibility and work efficiency in human type 2 diabetes using 16-[18F]fluoro-4-thiapalmitate, a novel PET fatty acid tracer.

Altered myocardial fuel selection likely underlies cardiac disease risk in diabetes, affecting oxygen demand and myocardial metabolic flexibility. We investigated myocardial fuel selection and metabolic flexibility in human type 2 diabetes mellitus (T2DM), using positron emission tomography to measure rates of myocardial fatty acid oxidation {16-[(18)F]fluoro-4-thia-palmitate (FTP)} and myocardial perfusion and total oxidation ([(11)C]acetate). Participants underwent paired studies under fasting conditions, comparing 3-h insulin + glucose euglycemic clamp conditions (120 mU·m(-2)·min(-1)) to 3-h saline infusion. Lean controls (n = 10) were compared with glycemically controlled volunteers with T2DM (n = 8). Insulin augmented heart rate, blood pressure, and stroke index in both groups (all P < 0.01) and significantly increased myocardial oxygen consumption (P = 0.04) and perfusion (P = 0.01) in both groups. Insulin suppressed available nonesterified fatty acids (P < 0.0001), but fatty acid concentrations were higher in T2DM under both conditions (P < 0.001). Insulin-induced suppression of fatty acid oxidation was seen in both groups (P < 0.0001). However, fatty acid oxidation rates were higher under both conditions in T2DM (P = 0.003). Myocardial work efficiency was lower in T2DM (P = 0.006) and decreased in both groups with the insulin-induced increase in work and shift in fuel utilization (P = 0.01). Augmented fatty acid oxidation is present under baseline and insulin-treated conditions in T2DM, with impaired insulin-induced shifts away from fatty acid oxidation. This is accompanied by reduced work efficiency, possibly due to greater oxygen consumption with fatty acid metabolism. These observations suggest that improved fatty acid suppression, or reductions in myocardial fatty acid uptake and retention, could be therapeutic targets to improve myocardial ischemia tolerance in T2DM.