Dietary management of peanut and tree nut allergy: what exactly should patients avoid?

Peanut and tree nut allergies are the commonest cause of life-threatening food-allergic reactions and significantly affect quality of life in children and their families. Dietary nut avoidance and provision of emergency medication is currently the mainstay of treatment. Nut avoidance has consequences on both quality of life and nutrition. We review the terminology that may cause confusion and lead to unnecessary dietary restrictions. In peanut or tree nut-allergic children, introduction of specific nuts to which the child is not allergic may improve quality of life and should be considered in patients with multiple foods allergies, vegan or ethnic-specific diets, in whom nuts are an important source of protein. Nut-allergic consumers do not just need to avoid foods containing nuts as an ingredient, but also contend with pre-packed foods which frequently have precautionary allergen labelling (PAL) referring to possible nut contamination. Although the published rate of peanut contamination in 'snack' foods with PAL (see Box ) ranges from 0.9-32.4%, peanut contamination in non-snack items with PAL is far less common. We propose that in some peanut-allergic patients (depending on history of reactivity to trace levels of peanut, reaction severity, other medical conditions, willingness to always carry adrenaline, etc.), consideration may be given to allow the consumption of non-snack foods containing PAL following discussion with the patient's (and their family's) specialist. More work is needed to provide consumers with clearer information on the risk of potential nut contamination in pre-packed food. We also draw attention to the change in legislation in December 2014 that require mandatory disclosure of allergens in non-pre-packed foods.

Unintended allergens in precautionary labelled and unlabelled products pose significant risks to UK allergic consumers.

BACKGROUND: Allergens in food may pose a risk to allergic consumers. While there is EU regulation for allergens present as an ingredient, this is not the case for unintended allergen presence (UAP). Food companies use precautionary allergen labels to inform allergic individuals of a potential risk from UAPs. This study investigates the risk of an allergic reaction within the milk-, wheat-, hazelnut- and peanut-allergic populations when ingesting UK foods across multiple product categories with and without precautionary allergen labelling. METHODS: Allergen risk assessment using probabilistic techniques enables the estimation of the residual risk after the consumption of a product that unintentionally contains an allergen. RESULTS: Within this selection of UK products, the majority that tested positive for an allergen contained a concentration of allergen predicted to cause a reaction in >1% of the allergic population. The concentrations of allergens measured were greater than the VITAL(®) 2.0 action levels and would trigger precautionary allergen labelling. This was found for products both with and without precautionary allergen labelling. CONCLUSIONS: The results highlight the need for the food industry and regulators to adopt a transparent, risk-based approach for the communication of the risk associated with potential cross-contact that could occur in the processing facility or production chain.

Precautionary allergen labelling: perspectives from key stakeholder groups.

Precautionary allergen labelling (PAL) was introduced by the food industry to help manage and communicate the possibility of reaction from the unintended presence of allergens in foods. However, in its current form, PAL is counterproductive for consumers with food allergies. This review aims to summarize the perspectives of all the key stakeholders (including clinicians, patients, food industry and regulators), with the aim of defining common health protection and risk minimization goals. The lack of agreed reference doses has resulted in inconsistent application of PAL by the food industry and in levels of contamination that prompt withdrawal action by enforcement officers. So there is a poor relationship between the presence or absence of PAL and actual reaction risk. This has led to a loss of trust in PAL, reducing the ability of consumers with food allergies to make informed choices. The result has been reduced avoidance, reduced quality of life and increased risk-taking by consumers who often ignore PAL. All contributing stakeholders agree that PAL must reflect actual risk. PAL should be transparent and consistent with rules underpinning decision-making process being communicated clearly to all stakeholders. The use of PAL should indicate the possible, unintended presence of an allergen in a consumed portion of a food product at or above any proposed action level. This will require combined work by all stakeholders to ensure everyone understands the approach and its limitations. Consumers with food allergy then need to be educated to undertake individualized risk assessments in relation to any PAL present.

Identification and characterization of intestinal lactobacilli strains capable of degrading immunotoxic peptides present in gluten.

AIM: Identify and characterize bacteria from the proximal gastrointestinal tract of pigs capable of degrading immunogenic gluten peptides. METHODS AND RESULTS: Bacteria were cultured from the small intestine of pigs fed a 20% gluten diet and from an enrichment media with the 18-mer peptide LQLQPFPQPQLPYPQPQL. Isolates were screened for the production of specialized proteolytic enzymes and the ability to degrade and remove metastable peptides from α-gliadin (16-mer and 33-mer) and ω-gliadin (17-mer), with established roles in the aetiology of coeliac disease. Degradation was determined by ELISA and mass spectrometry (UHPLC-MS/MS in MRM mode), and hydrolysis fragments were characterized by LC-MS/MS. Four strains from the species Lactobacillus ruminis, Lactobacillus johnsonii, Lactobacillus amylovorus and Lactobacillus salivarius showed the highest peptide-degrading activities. Strains displayed different degradation rates and cleavage patterns that resulted in reduction but not complete removal of immunotoxic epitopes. CONCLUSIONS: We employed a unique enrichment process to select for bacteria adapted to the conditions of the proximal gastrointestinal tract with the ability to partially detoxify well-characterized peptides involved in coeliac disease. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides a basis for the selection of Lactobacillus strains for probiotic applications aimed to reduce epitope-containing gluten peptides before reaching the epithelium of the small intestine of patients with coeliac disease.

Clostridium difficile as a cause of healthcare-associated diarrhoea among children in Auckland, New Zealand: clinical and molecular epidemiology.

We aimed to determine the incidence of Clostridium difficile infection (CDI), the molecular epidemiology of circulating C. difficile strains and risk factors for CDI among hospitalised children in the Auckland region. A cross-sectional study was undertaken of hospitalised children <15 years of age in two hospitals investigated for healthcare-associated diarrhoea between November 2011 and June 2012. Stool specimens were analysed for the presence of C. difficile using a two-step testing algorithm including polymerase chain reaction (PCR). C. difficile was cultured and PCR ribotyping performed. Demographic data, illness characteristics and risk factors were compared between children with and without CDI. Non-duplicate stool specimens were collected from 320 children with a median age of 1.2 years (range 3 days to 15 years). Forty-six patients (14 %) tested met the definition for CDI. The overall incidence of CDI was 2.0 per 10,000 bed days. The percentage of positive tests among neonates was only 2.6 %. PCR ribotyping showed a range of strains, with ribotype 014 being the most common. Significant risk factors for CDI were treatment with proton pump inhibitors [risk ratio (RR) 1.74, 95 % confidence interval (CI) 1.09-5.59; p = 0.002], presence of underlying malignancy (RR 2.71, 95 % CI 1.65-4.62; p = 0.001), receiving chemotherapy (RR 2.70, 95 % CI 1.41-4.83; p = 0.003) and exposure to antibiotics (RR 1.17, 95 % CI 0.99-1.17; p = 0.03). C. difficile is an important cause of healthcare-associated diarrhoea in this paediatric population. The notion that neonatal populations will always have high rates of colonisation with C. difficile may not be correct. Several risk factors associated with CDI among adults were also found to be significant.

Sex and pubertal variation in reward-related behavior and neural activation in early adolescents.

This study aimed to characterize the role of sex and pubertal markers in reward motivation behavior and neural processing in early adolescence. We used baseline and two-year follow-up data from the Adolescent Brain and Cognitive DevelopmentSM study (15844 observations; 52% from boys; age 9-13). Pubertal development was measured with parent-reported Pubertal Development Scale, and DHEA, testosterone, and estradiol levels. Reward motivation behavior and neural processing at anticipation and feedback stages were assessed with the Monetary Incentive Delay task. Boys had higher reward motivation than girls, demonstrating greater accuracy difference between reward and neutral trials and higher task earnings. Girls had lower neural activation during reward feedback than boys in the nucleus accumbens, caudate, rostral anterior cingulate, medial orbitofrontal cortex, superior frontal gyrus and posterior cingulate. Pubertal stage and testosterone levels were positively associated with reward motivation behavior, although these associations changed when controlling for age. There were no significant associations between pubertal development and neural activation during reward anticipation and feedback. Sex differences in reward-related processing exist in early adolescence, signaling the need to understand their impact on typical and atypical functioning as it unfolds into adulthood.

Challenges in testing genetically modified crops for potential increases in endogenous allergen expression for safety.

Premarket, genetically modified (GM) plants are assessed for potential risks of food allergy. The major risk would be transfer of a gene encoding an allergen or protein nearly identical to an allergen into a different food source, which can be assessed by specific serum testing. The potential that a newly expressed protein might become an allergen is evaluated based on resistance to digestion in pepsin and abundance in food fractions. If the modified plant is a common allergenic source (e.g. soybean), regulatory guidelines suggest testing for increases in the expression of endogenous allergens. Some regulators request evaluating endogenous allergens for rarely allergenic plants (e.g. maize and rice). Since allergic individuals must avoid foods containing their allergen (e.g. peanut, soybean, maize, or rice), the relevance of the tests is unclear. Furthermore, no acceptance criteria are established and little is known about the natural variation in allergen concentrations in these crops. Our results demonstrate a 15-fold difference in the major maize allergen, lipid transfer protein between nine varieties, and complex variation in IgE binding to various soybean varieties. We question the value of evaluating endogenous allergens in GM plants unless the intent of the modification was production of a hypoallergenic crop.

Sequence variation in the human angiotensin converting enzyme.

Angiotensin converting enzyme (encoded by the gene DCP1, also known as ACE) catalyses the conversion of angiotensin I to the physiologically active peptide angiotensin II, which controls fluid-electrolyte balance and systemic blood pressure. Because of its key function in the renin-angiotensin system, many association studies have been performed with DCP1. Nearly all studies have associated the presence (insertion, I) or absence (deletion, D) of a 287-bp Alu repeat element in intron 16 with the levels of circulating enzyme or cardiovascular pathophysiologies. Many epidemiological studies suggest that the DCP1*D allele confers increased susceptibility to cardiovascular disease; however, other reports have found no such association or even a beneficial effect. We present here the complete genomic sequence of DCP1 from 11 individuals, representing the longest contiguous scan (24 kb) for sequence variation in human DNA. We identified 78 varying sites in 22 chromosomes that resolved into 13 distinct haplotypes. Of the variant sites, 17 were in absolute linkage disequilibrium with the commonly typed Alu insertion/deletion polymorphism, producing two distinct and distantly related clades. We also identified a major subdivision in the Alu deletion clade that enables further analysis of the traits associated with this gene. The diversity uncovered in DCP1 is comparable to that described for other regions in the human genome. The highly correlated structure in DCP1 raises important issues for the determination of functional DNA variants within genes and genetic studies in humans based on marker association.

DNA sequence diversity in a 9.7-kb region of the human lipoprotein lipase gene.

Lipoprotein lipase plays a central role in lipid metabolism and the gene that encodes this enzyme (LPL) is a candidate susceptibility gene for cardiovascular disease. Here we report the complete sequence of a fraction of the LPL gene for 71 individuals (142 chromosomes) from three populations that may have different histories affecting the organization of the sequence variation. Eighty-eight sites in this 9.7 kb vary among individuals from these three populations. Of these, 79 were single nucleotide substitutions and 9 sites involved insertion-deletion variations. The average nucleotide diversity across the region was 0.2% (or on average 1 variable site every 500 bp). At 34 of these sites, the variation was found in only one of the populations, reflecting the differing population and mutational histories. If LPL is a typical human gene, the pattern of sequence variation that exists in introns as well as exons, even for the small number of samples considered here, will present challenges for the identification of sites, or combinations of sites, that influence variation in risk of disease in the population at large.

Sex and pubertal influences on the neurodevelopmental underpinnings of schizophrenia: A case for longitudinal research on adolescents.

Sex is a significant source of heterogeneity in schizophrenia, with more negative symptoms in males and more affective symptoms and internalizing comorbidity in females. In this narrative review, we argue that there are likely sex differences in the pathophysiological mechanisms of schizophrenia-spectrum disorders (SZ) that originate during puberty and relate to the sex-specific impacts of pubertal maturation on brain development. Pubertal maturation might also trigger underlying (genetic or other) vulnerabilities in at-risk individuals, influencing brain development trajectories that contribute to the emergence of SZ. This review is the first to integrate links between pubertal development and neural development with cognitive neuroscience research in SZ to form and evaluate these hypotheses, with a focus on the frontal-striatal and frontal-limbic networks and their hypothesized contribution to negative and mood symptoms respectively. To test these hypotheses, longitudinal research with human adolescents is needed that examines the role of sex and pubertal development using large cohorts or high risk samples. We provide recommendations for such studies, which will integrate the fields of psychiatry, developmental cognitive neuroscience, and developmental endocrinology towards a more nuanced understanding of the role of pubertal factors in the hypothesized sex-specific pathophysiological mechanisms of schizophrenia.

Abnormal liver function tests in acne patients receiving isotretinoin.

BACKGROUND: Isotretinoin is an efficacious treatment option for severe acne. Although isotretinoin often causes mild liver enzyme elevation, how acne patients should be monitored on isotretinoin therapy is not well characterized. OBJECTIVE: The purpose of this study was to assess the management and clinical outcome of acne patients with abnormal aspartate transaminase (AST) and alanine aminotransferase (ALT) when receiving isotretinoin. METHODS: A retrospective chart review was conducted in acne subjects with abnormal AST and ALT levels receiving isotretinoin. Abnormal liver enzymes were graded using the Common Terminology Criteria for Adverse Events version 5. RESULTS: Of 108 subjects with abnormal liver enzymes, 79 subjects were on isotretinoin 80 mg and 23 subjects were on isotretinoin 40 mg. Most abnormalities were during Month 1 of therapy (48). Of the 122 abnormal Grade 1 AST elevations, 40 normalized, 38 remained in Grade 1, and 1 increased into Grade 2 when a healthcare provider maintained the isotretinoin dose. Of the 102 abnormal Grade 1 ALT levels managed by maintaining the isotretinoin dose, 31 normalized and 38 remained persistently elevated. CONCLUSION: Most mild elevations of isotretinoin therapy do not worsen. Acne patients with isotretinoin may not need continued testing when experiencing low-grade liver enzyme abnormalities.

Complete globozoospermia associated with PLCζ deficiency treated with calcium ionophore and ICSI results in pregnancy.

Globozoospermia is an infrequent pathology in which spermatozoa lack acrosomes. Patients are considered sterile without IVF augmented with intracytoplasmic sperm injection (ICSI), as fertilization is impaired due to absence of oocyte activation. As far as is known, this is the first study to report results of a comprehensive approach to the treatment of the semen parameters, sperm DNA fragmentation, aneuploidy, transmission electron microscopy, Western blotting and immunofluorescence for detection of phospholipase C zeta (PLCzeta), as well as ICSI outcome, of an affected patient. Morphological evaluation and transmission electron microscopy revealed complete globozoospermia with significant duplicate heads and tails. Analysis for DNA damage revealed fragmentation rates of approximately 80% in semen and 15-23% in swim-up fractions. PLCzeta was not detected by immunofluorescence or Western blotting. Aneuploidy rates were within normal ranges. ICSI followed by oocyte activation with calcium ionophore resulted in high rates of fertilization, and an ongoing pregnancy was established after transfer of cryopreserved-thawed embryos.

Health behaviour models: a framework for studying adherence in children with atopic dermatitis.

Atopic dermatitis (AD) is a common problem of childhood causing considerable distress. Effective topical treatments exist, yet poor adherence often results in poor outcomes. A framework is needed to better understand adherence behaviour. To provide a basis for this framework, we reviewed established models used to describe health behaviour. Structural elements of these models informed the development of an adherence model for AD that can be used to complement empirical AD treatment trials. Health behaviour models provide a means to describe factors that affect adherence and that can mediate the effects of different adherence interventions. Models of adherence behaviour are important for promoting better treatment outcomes for children with AD and their families. These models provide a means to identify new targets to improve adherence and a guide for refining adherence interventions.

Clinical relevance of sensitization to lupine in peanut-sensitized adults.

BACKGROUND: The use of lupine in food has been increasing during the last decade and allergic reactions to lupine have been reported, especially in peanut-allergic patients. The frequency and the degree of cross-reactivity to other legumes are not known. The aim of the study was to investigate the frequency of sensitization to lupine, and in addition to pea and soy, and its clinical relevance, in peanut-sensitized patients. Furthermore, to determine the eliciting dose (ED) for lupine using double-blind placebo-controlled food challenges (DBPCFC). METHODS: Thirty-nine unselected peanut-sensitized patients were evaluated by skin prick tests (SPT) and ImmunoCAP to lupine, pea, and soy. Clinical reactivity was measured by DBPCFC for lupine, and by history for pea and soy. RESULTS: Eighty-two percent of the study population was sensitized to lupine, 55% to pea, and 87% to soy. Clinically relevant sensitization to lupine, pea, or soy occurred in 35%, 29%, and 33% respectively of the study population. None of the patients was aware of the use of lupine in food. The lowest ED for lupine, inducing mild subjective symptoms, was 0.5 mg, and the no observed adverse effect level (NOAEL) was 0.1 mg. No predictive factors for lupine allergy were found. CONCLUSION: In peanut-sensitized patients, clinically relevant sensitization to either lupine or to pea or soy occurs frequently. The ED for lupine is low (0.5 mg), which is only fivefold higher than for peanut. Patients are not aware of lupine allergy and the presence of lupine in food, indicating that education is important to build awareness.

Thresholds for food allergens and their value to different stakeholders.

Thresholds constitute a critical piece of information in assessing the risk from allergenic foods at both the individual and population levels. Knowledge of the minimum dose that can elicit a reaction is of great interest to all food allergy stakeholders. For allergic individuals and health professionals, individual threshold data can inform allergy management. Population thresholds can help both the food industry and regulatory authorities assess the public health risk and design appropriate food safety objectives to guide risk management. Considerable experience has been gained with the double-blind placebo-controlled food challenge (DBPCFC), but only recently has the technique been adapted to provide data on thresholds. Available data thus vary greatly in quality, with relatively few studies providing the best quality individual data, using the low-dose DBPCFC. Such high quality individual data also form the foundation for population thresholds, but these also require, in addition to an adequate sample size, a good characterization of the tested population in relation to the whole allergic population. Determination of thresholds at both an individual level and at a population level is influenced by many factors. This review describes a low-dose challenge protocol developed as part of the European Community-funded Integrated Project Europrevall, and strongly recommends its wider use so that data are generated that can readily increase the power of existing studies.

Enhanced selective extraction of hexane from hexane/soybean oil mixture using binary gas mixtures of carbon dioxide.

Carbon dioxide (CO2) can effectively separate hexane from a mixture of soybean oil (SBO) and hexane with a slight coextraction of SBO. Previous research demonstrated that CO2 entrained with helium significantly reduced SBO solubility in CO2. In this study, CO2 was mixed with three gases (He, N2, or Ar) (0.5-30 vol %) to decrease SBO solubility while attempting to maintain hexane solubility. The binary gas mixtures (at 25 degrees C and 9.31 MPa) were passed through a 25 wt % hexane/SBO mixture inside a 2.5 m fractionation column. Coextracted SBO was inversely proportional to binary gas concentration, whereas residual hexane in the raffinate was proportional to binary gas concentration. The 10% binary mixture of N2 or Ar was the best compromise to obtain both low residual hexane levels (i.e., 26 ppm) and low SBO coextraction (i.e., only 40 mg). This carry-over of SBO represents a 95% reduction in SBO carry-over compared to neat CO2.

Hazard characterisation in food allergen risk assessment: the application of statistical approaches and the use of clinical data.

A structured approach to assess the risk to allergic individuals from food allergens requires as a first step the experimental measurement of minimum eliciting doses in a population that is as representative as possible of the relevant allergic population, using a standardised protocol. These doses are established in controlled challenge studies, but logistical and statistical constraints mean that a proportion of the allergic population may still be at risk of reacting at doses below those which have been or could feasibly be tested. However, statistical modelling of the dose distribution resulting from such challenges permits inferences to be drawn about the proportion of allergic individuals that are likely to react to specified (low) amounts of residual allergen in food. However, different statistical models, which all provide good fits to the experimental data yield different values outside the experimental range. Consequently, the outputs from these models require a form of validation, which demonstrates how close the predictions are to reality. In addition to characterisation of the hazard, for each allergenic food this validation requires information about exposure to undeclared allergen, the actual number of reactions taking place in the wider allergic population, and the prevalence of allergy to that food.

Perfusion and Volume Response of Canine Brain Tumors to Stereotactic Radiosurgery and Radiotherapy.

BACKGROUND: Stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) are highly conformal, high-dose radiation treatment techniques used to treat people and dogs with brain tumors. OBJECTIVES: To evaluate the response to SRS- and SRT-treated tumors using volume and perfusion variables and to measure the survival times of affected dogs. ANIMALS: Prospective study of 34 dogs with evidence of brain tumors undergoing stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT). METHODS: Computed tomography and MRI imaging were used to calculate tumor volume and perfusion at baseline, and at 3 months and 6 months after treatment. Survival analysis was performed to evaluate treatment efficacy. RESULTS: Mean tumor volume significantly declined from baseline to the first recheck by -0.826 cm(3) (95% CI: -1.165, -0.487) (P < .001); this reduction was maintained at the second recheck. Blood flow and blood volume declined significantly in the tumor after treatment. Median survival was 324 days (95% CI: 292.8, 419.4), and 4 dogs survived longer than 650 days. Neither actual tumor volume (hazard ratio = 1.21, P = .19) nor the change in tumor volume from the baseline (hazard ratio = 1.38, P = .12) significantly affected the hazard of death because of the tumor. CONCLUSIONS AND CLINICAL IMPORTANCE: Stereotactic radiosurgery and SRT are effective treatments for reducing tumor volume, blood flow, and blood volume. Treated dogs surviving for more than 1 year are more likely to die from other causes than of their primary brain tumor. SRS and SRT should be considered for noninvasive treatment of intracranial brain tumors.