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Preventing nosocomial infection is a major unmet need of our times. Existing air decontamination technologies suffer from demerits such as toxicity of exposure, species specificity, noxious gas emission, environment-dependent performance and high power consumption. Here, we present a novel technology called “ZeBox” that transcends the conventional limitations and achieves high microbicidal efficiency. In ZeBox, a non-ionizing electric field extracts naturally charged microbes from flowing air and deposits them on engineered microbicidal surfaces. The surface’s three dimensional topography traps the microbes long enough for them to be inactivated. The electric field and chemical surfaces synergistically achieve rapid inactivation of a broad spectrum of microbes. ZeBox achieved near complete kill of airborne microbes in challenge tests (5–9 log reduction) and $$>90\%$$ > 90 % efficiency in a fully functional stem cell research facility in the presence of humans. Thus, ZeBox fulfills the dire need for a real-time, continuous, safe, trap-and-kill air decontamination technology.

Oral food challenge is the gold standard in diagnosing food allergies; however, many testing protocols are available. The present article illustrates the difficulties associated with interpreting oral challenge tests with the example of a six-year-old boy with allergy to hen's eggs. The symptoms observed on the first day of challenge indicated a negative result; however, the consumption of the cumulative dose resulted in anaphylaxis. The interpretation of the oral food challenge can be complicated. The criteria used to determine a positive or negative result are sometimes ambiguous. An accurate interpretation of the results is key to determining correct management in children with food allergy.

Clostridioides difficile is a dangerous human pathogen because it can grow to high numbers in the intestine, cause colitis with its potent toxins, and persist as spores. C. difficile infection (CDI) is the primary hospital-acquired infection in North America and Europe, and it now is a global disease. Even with newer laboratory tests, there still is confusion on accurately diagnosing this disease. Three guidelines from three different healthcare-affiliated societies have recently been published. Consensus consolidated recommendations from these guidelines should be recognized by healthcare professionals, who need to understand why this disease continues to be difficult to diagnose and need a clear understanding of the advantages and limitations of current tests. Hopefully, these combined efforts will lead to an improvement in the recognition of this pathogen and a reduction in the suffering and economic loss caused by CDI.

Cough sensitivity can be described as the reaction intensity of the cough reflex to different stimuli which activate chemically and mechanically sensitive vagal afferent nerves innervating airways and lungs. Measurement of cough reflex sensitivity plays an important role in revealing the underlying mechanisms of cough and evaluating the effects of pharmacological interventions. Besides, different responses to cough suppression therapies indicate the existence of cough hypersensitivity. In consideration of these factors stated above, cough sensitivity should therefore be assessed with a variety of cough challenge tests. Based on the neuroanatomical characteristics of the cough reflex, chemical challenge tests have been developed to objectively assess cough sensitivity. In cough inhalation challenges, capsaicin and citric acid are commonly used as the tussive agents to induce cough, which are validated for describing a profile of cough sensitivity to chemical irritants. Recently, mechanical methodologies have also been tried to measure the mechanical sensitivity of the cough reflex. Methodological consideration and selection are necessary for the reasonable assessment of cough sensitivity while employing cough challenges in clinical trials. Thus, in this review, we will focus on describing various methodologies of cough sensitivity measurement and, detailing some factors influencing on the accuracy of outcomes in the experimentally induced cough.

Aim: Oral food challenges (OFCs) and drug provocation tests (DPTs) are currently the gold standards for evaluating food and drug hypersensitivity, respectively; however, use of these tests on children may generate anxiety and depression among their parents. Our aim was to explore depression and anxiety level among parents of children who were undergoing clinical evaluation via a DPT or OFC. Methods: This cross-sectional study included parents of patients diagnosed with food or drug hypersensitivity reactions in the pediatric allergy clinic between September 2018 and October 2019. Children in Group 1 were subjected to DPT, Group 2 underwent OFC, and Group 3 were healthy controls. Before a child underwent an OFC or DPT, all parents (one parent per child) completed the Hospital Anxiety and Depression Scale, which is a serial assessment for symptoms of depression and anxiety. Results: The study included parents of 105 children, among which Group 1 (n=50 children) were subjected to DPT, Group 2 (n =35 children) underwent OFC, and Group 3 (n=20 children) were healthy controls. In all three Groups, parents were primarily female (62.9%). Anxiety and depression scores were significantly higher among the parents of children in Groups 1 and 2 vs. those of children in Group 3 (P=0.002 and P=0.028, respectively). Anxiety scores were significantly higher among parents of children in Group 2 than those of children in Group 1 (P=0.017). Conclusions: DPTs and OFCs have a significant impact on the emotional status of parents. Parents of children with suspected or documented food allergy experience particularly elevated levels of anxiety and depression before an OFC.

Background There are insufficient published data on the prevalence of cow's milk protein allergy (CMPA) in Egypt. Aim of the Work The study aims to estimate the frequency of CMPA among young Egyptian children in a trial to delineate the magnitude of the problem in our population. Methods A cross-sectional, observational study was conducted on 500 young Egyptian children from the general population aged from 6 months to 5 years; 200 males and 300 females. Children were subjected to history taking and clinical examination. Suspected cases with suggestive clinical history of CMPA were subjected to skin prick test (SPT) with standardized cow’s milk protein allergen extract and open oral challenge test (OCT). Results In the present study, 6.2% of screened children had positive clinical history suggestive of CMPA, 35.5% of them had positive SPT and 51.6% had positive OCT. Based on clinical history and OCT, 3.2% were documented to have CMPA, 3% had undocumented CMPA or low probability of CMPA and 93.8% had no CMPA. The highest rate of initial onset of CMPA is seen before the first year of life (96.8%) and 81.3% of children with positive OCT were formula/mixed-fed. The clinical manifestations in infants with suspected CMPA were variable, and the main presenting feature was gastrointestinal tract manifestations (42%). The IgE-mediated CMPA was more common and constituted 56.3% of the CMPA cases. Conclusion The frequency of CMPA among Egyptian children up to 5 years of age is comparable to the reported frequencies worldwide. IgE-mediated CMPA accounts for more than 2/3 of the patients with proven CMPA in this study.

Shelf‐life studies in ready‐to‐eat (RTE) modified atmosphere packaged (MAP) precut iceberg lettuce (minimally processed) were carried out in order to evaluate the natural microflora of the product and survival or multiplication of Listeria monocytogenes (L. monocytogenes), taking into consideration the impact of the production steps resulting in a reduction of the shelf life of the fresh‐cut produce, due to the accelerated enzymatic activity, moisture loss, and microbial proliferation. The research first aimed to evaluate the characteristics of the natural microflora of the product, and then, L. monocytogenes dynamics were studied via challenge tests. L. monocytogenes concentration was studied at 8 and 12°C storage temperature for 10 days, 6 days longer than their shelf life. The number of L. monocytogenes in samples stored both at 8°C and 12°C increased gradually, more evidently in samples stored at 12°C. L. monocytogenes dynamics were studied to define maximum growth rate (μmax) at 8°C (0.0104 log10CFU/g/h) and 12°C (0.0183 log10CFU/g/h). Data obtained from the study were used to develop and validate a specific predictive model able to predict the behavior of L. monocytogenes in RTE MAP iceberg lettuce. According to the model, an increase in storage temperature of 6°C (e.g., from 8 to 14°C) would lead to an increase in L. monocytogenes concentration of more than 6 log10CFU/g at the 10th day of the challenge test (12th days of shelf life). Storage at 4°C allowed to increase L. monocytogenes enumeration from 3.30 log10CFU/g at D0 to 3.60 log10CFU/g at D10. The model could be applied to microorganisms other than L. monocytogenes, modifying the coefficients of the polynomial equation on which it is based., Shelf‐life studies in ready‐to‐eat (RTE) modified atmosphere packaged (MAP) precut iceberg lettuce were carried out in order to evaluate the natural microflora of the product and survival or multiplication of Listeria monocytogenes. Data obtained from the study were used to develop and validate a specific predictive model able to predict the behavior of L. monocytogenes in this product.

Bulimia Nervosa (BN) is a serious eating disorder, which affects 0.8-2.9% of the young population. The etiology is unknown and biomarkers would support in understanding the pathophysiology of BN, and in identifying BN patients that may benefit from medical treatment. This systematic review aims to answer whether (a) BN deviate from healthy controls in terms of serotonin (5-HT) biomarkers in blood, and whether (b) blood-based 5-HT biomarkers could be used to tailor psychopharmacological treatment in BN. A literature search using PubMed, PsycINFO and Embase was done using the following search terms: "Bulimia Nervosa" AND "serotonin" AND "blood" OR "plasma" OR "serum". 32 studies were included in this systematic review. Several biomarkers and challenge tests were identified and all studies described an association with BN and dysregulation of the 5-HT system compared to healthy controls. Several studies pointed to an association also to borderline symptoms in BN. BN deviate from healthy controls in terms of 5-HT biomarkers in blood supporting an abnormal 5-HT system in BN. 5-HT biomarkers and associated methods could be used to tailor treatment in BN although as yet, most tests described are unpractical for bedside use.

Chronic inducible urticarias are characterized by the risks of systemic reactions and a significant impairment of patient’s quality of life. The diagnosis of chronic inducible urticarias relies on the patient’s history and the challenge tests. A treatment algorithm for the management of chronic inducible urticarias includes nonsedating antihistamines as a first-line treatment. The international guidelines for the management of chronic inducible urticarias recommend updosing of nonsedating antihistamines up to four fold if standard doses are not effective. The meta-analysis suggests the efficacy of omalizumab in chronic inducible urticarias. In the prospect, the novel options of biological therapy for chronic inducible urticarias are expected.

Bronchoprovocation inhalation challenge tests with direct acting stimuli (e.g. methacholine) are widely used clinically to aid in the diagnosis of asthma. Areas covered: The history of direct challenges with histamine and muscarinic agonists is reviewed. This began with parenteral administration of stimuli with responses monitored clinically and by VC, progressing to inhalation dose-response challenges monitored by FEVThe methacholine inhalation test is highly sensitive for a diagnosis of current asthma when symptoms under evaluation are clinically current and when methacholine is inhaled without deep inhalations. Under these circumstances, a methacholine PD

The controlled drug exposure test (DPT) is currently considered the gold standard for the diagnosis of drug allergy. Drug-induced adverse reactions (ADRs) are a growing reason for consultation in both primary and specialized care. Allergology consultations in Spain are the ones that usually study these ADRs and rule out immunological mechanisms involved in up to 90% of the cases consulted. An adequate approach to these cases has an obvious impact on the costs and efficacy of the treatments required by other specialists, so that if we did not use DPTs, patients would require more expensive, more toxic and less effective treatments in most of the cases. In recent years, a large number of new drugs have been developed and this document is intended to be a practical guide in the management of PDT with the vision of the Spanish Allergology Society. Diagnostic work begins with a detailed history of the patient. Skin tests are only useful for some medications, and in most cases the diagnosis can only be confirmed by DPT. Although there is usually cross-reactivity, DPTs can confirm the diagnosis and also help to find a tolerable alternative drug. The individual management of patients in a programmed way, taking into account both the type of drug to be studied and the patient´s comorbidities, usually allows a solution to be found for the majority of patients.

Cow’s Milk protein allergy (CMA) is a common finding in infants and young children (2-3%). Its diagnosis is a multifaceted aspect including medical history, clinical examination, diagnostic elimination diets, oral challenge tests (OCT), skin prick tests (SPTs) and specific immunoglobulin E (sIgE) measurements. We aimed to assess the value of SPT and sIgE for diagnosis of infants with CMA in routine clinical practice. This cross sectional study included 102 infants with suspected CMA. They were subjected to OCT, SPT with pasteurized cow's milk and measurement of serum sIgE for cow’s milk by immunoblot technique. Seventy-two infants (70.59%) showed positive allergic reactions with OCT. Comparing SPT to OCT, sensitivity was 75%, specificity was 68.7%, predictive value for negative (PVN) was 59% and predictive value for positive (PVP) was 93.1%. Comparing sIgE to OCT, sensitivity was 68.1%, specificity was 96.7%, PVN was 69% and PVP was 98%. Comparing both SPT and sIgE together to OCT, sensitivity was 62.5%, specificity was 96.6%, PVN was 51.8% and PVP was 97.8%. For clinical practice, our findings suggest that correlation between SPT and sIgE is significant regarding CMA diagnosis. Therefore, these tests can be used together for diagnosis of CMA. However, still some cases can be only diagnosed with positive OCT with non-detectable sensitization. Therefore, a detailed history is a major factor in assessing CMA. In addition, definition of new optimal cut-offs for sIgE and SPT to cow’s milk can improve the accuracy of these tests, hoping to avoid unnecessary and potentially dangerous OTC.

OBJECTIVE We aimed to analyse the pre-analytical process and its effect of 50 g of oral glucose challenge test results for screening gestational diabetes mellitus. RESEARCH DESIGN AND METHODS The 50 g oral glucose challenge test was performed to 30 pregnant women, and the blood was collected as two samples for three tubes containing; serum separating jell (SSJ), sodium fluoride-potassium oxalate (NaF - KOx) and sodium citrate-containing tube. The first samples of the three tubes were centrifuged within 30 minutes, and second samples were centrifuged after 60 minutes and were analysed. One sample in SSJ tube and was analysed in the same day according to hospitals routine practice. The results were compared. RESULTS Among the 30 samples, the mean decrease in glucose levels was highest in the SSJ tube (0.38 mmol/L), followed by 0.16 mmol/L in Na citrate tube and 0.14 mmol/L in NaF-KOx tube. The hospital routine assessment with SSJ was 6.36 ± 1.90 mmol/L. The 60 minutes glucose results were 6.80 ± 1.88 mmol/L vs 6.42 ± 1.97 mmol/L for SSJ, 5.95 ± 1.60 mmol/L vs 5.78 ± 1.51 mmol/L for Na Citrate and 6.90 ± 1.86 mmol/L vs 6.75 ± 1.90 mmol/L for NaF-KOx mg/dL groups, respectively, and both the changes within time and the results between the tubes showed a statistically significant difference (P

Summary : The aphthovirus subtype Asia 1/2 (strain India 21/80) recovered in India was further characterized by microneutrali zation, guinea pig protection and challenge tests in cattle. These tests confirmed it to differ from subtype Asia 1/1 and corroborated the results of microcompleme nt fixation tests. It multiplied to high titre in BHK21 cell culture. A PEG-concentrat ed vaccine was prepared using this strain, which when tested in cattle proved to be highly immunogenic and protective in a 1 ml dose. The studies also demonstrated that it is possible to readily adapt an indigenous strain and manufacture an effective vaccine in a short time to meet the need of an effective control of FMD in a given area.

Antikoaguliantai yra plati medikamentų grupė, priklausanti skirtingoms farmakologinėms grupėms, turinti skirtingus veikimo mechanizmus ir galinti sukelti skirtingas nepageidaujamas imunines reakcijas. Nors antikoaguliantai retai sukelia alergines reakcijas, tačiau jos gali būti sunkios ir kelti pavojų gyvybei. Dažniausiai pasireiškia lėtosios padidėjusio jautrumo reakcijos, rečiau – II tipo (heparino indukuota trombocitopenija) bei greitojo tipo padidėjusio jautrumo reakcijos. Nepageidaujamų imuninių reakcijų antikoaguliantams diagnostika remiasi būdingais klinikiniais požymiais, odos alerginiais mėginiais bei provokaciniais mėginiais.

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior In this study, dry inocula were developed using four different carriers [talc, fine sand (0.05–0.2 mm), regular sand (0.2–0.6 mm), and calcium carbonate] for validation of inactivation steps of low moisture foods against Salmonella enterica. Besides, the changes in aw and the survival of S. enterica in the dry inocula made with the four carriers were evaluated throughout the storage period of up to 150–180 days at 4 and 25 °C. Among the carriers evaluated fine and regular sand seem to constitute the best carrier agents for longer preservation of S. enterica cells to be employed in dry inocula. Besides, the storage of inoculated carrier agents under refrigeration (4 °C) enhanced the stability of the dry inocula prepared, maintaining S. enterica counts unaltered for ~ six months (p < 0.05). Overall, based on the results, it has been found that the aw variation during storage did not directly influence S. enterica survival in the dry inocula. However, considering only the aw of the dry inocula obtained using the different carrier agents, it is possible to propose combinations between carrier agents and aw of low moisture foods (LMF). The findings of this study will be highly relevant for the development of stable dry inocula for use in the validation of the inactivation steps of LMF.

Cold smoked salmon and sushi salmon have been implicated in outbreaks of listeriosis. We performed challenge tests and a durability study with Listeria monocytogenes on different salmon products to determine the growth potential of this important food-borne pathogen. Data from the challenge test showed a significant growth potential of L. monocytogenes on all of the tested salmon products, with faster growth in sushi salmon than in cold smoked salmon. In identical products that were naturally contaminated at low levels, the durability study did not confirm a high growth potential, possibly due to interactions with competing microflora. The injection of sodium lactate (NaL) at a high concentration (30%) into cold smoked salmon significantly reduced the growth potential of L. monocytogenes. In addition to good manufacturing practices, the injection of higher concentrations of NaL may therefore be a useful additional hurdle to prevent growth of L. monocytogenes to high numbers in the tested salmon products.

National programs for foot-and-mouth disease (FMD) eradication includes the use of vaccination; Turkey which is endemic to FMD virus (FMDV) (except for the Thrace region) and there is a risk of incursion of exotic strains from eastern borders. In 2015, a devastating outbreak was caused by the A/ASIA/G-VII (G-VII) lineage, which led to the inclusion of a new vaccine strain (A/TUR/15) derived from this lineage in 3 months. Although most of the cattle population in Turkey was then immunized with A/TUR/15 (vaccine coverage: 92.8%), the G-VII lineage continued to cause outbreaks in the field despite the evidence of protection observed with A/TUR/15 in in vivo and in vitro tests. When G-VII field strains were examined, changes in their genomes were detected. As the lineage appeared to be evolving, an unconventional vaccination strategy was adapted which changed the vaccine strain with new variants of G-VII according to antigenic evolution. To assess the suitability of candidate vaccine strains derived from the variants of the G-VII lineage, three viral candidates were assessed (A/TUR/15, A/TUR/16 and A/TUR/17) by in vitro virus neutralization tests for r1 vaccine matching and in vivo heterologous challenge tests. Although all three vaccine strains were antigenically well matched with each other and other G-VII field viruses, due to continues outbreaks the vaccine strain was changed three times in 20 months from A/TUR/15 (Dec 2015) to A/TUR/16 (Dec 2016) and then to A/TUR/17 (Aug 2017). With this strategy serotype A has not been observed in the field since January 2018. This study highlights the importance of adapting the vaccine strains according to antigenic evolution as this could be a valuable combat strategy in endemic countries, rather than using well-known vaccine strain and relying only on the relationship coefficient (r1 ) value.

Objective To evaluate the positivity of challenge tests of patients suspected of chronic inducible urticaria and the response to treatment. Methods A retrospective study of electronic medical records of patients suspected of chronic inducible urticaria. All patients were submitted to challenge tests with triggering stimuli, according to the clinical history and, subsequently, the response to drug treatment was evaluated. Results A total of 191 patients with suspected chronic inducible urticaria were included. It was confirmed in 118 patients and 122 positive tests (4 patients with 2 different positive tests). Most had dermographic urticaria (70.3%), followed by cholinergic urticaria (17.8%). Regarding treatment, 28% responded to antihistamine in licensed doses, 34.7% with increased doses, 9.3% responded to the addition of another medication. The concomitance of chronic inducible urticaria and chronic spontaneous urticaria was found in 35.3% of patients, being more frequent in females, with longer time to control symptoms and higher frequency of cholinergic urticaria. Conclusion The confirmation of chronic inducible urticaria in patients with this suspicion, after challenge tests, was high. There was a good response to antihistamine. In the concomitance of chronic spontaneous urticaria, longer time to control symptoms and higher frequency of cholinergic urticaria were observed. RESUMO Objetivo Avaliar a positividade dos testes de provocação de pacientes com suspeita de urticária crônica induzida e sua resposta ao tratamento. Métodos Estudo retrospectivo de prontuários eletrônicos de pacientes com suspeita de urticária crônica induzida. Todos os pacientes foram submetidos aos testes de provocação com estímulos desencadeantes, conforme história clínica e, posteriormente, foi avaliada a resposta ao tratamento medicamentoso. Resultados Foram incluídos 191 pacientes com suspeita de urticária crônica induzida, a qual foi confirmada em 118 pacientes e 122 testes positivos (4 pacientes com 2 testes positivos diferentes). A maioria apresentava urticária dermográfica (70,3%), seguida de urticária colinérgica (17,8%). Em relação ao tratamento, 28% responderam ao anti-histamínico em doses licenciadas, 34,7% em doses aumentadas e 9,3% responderam à adição de outro medicamento. A concomitância de urticária crônica induzida com urticária crônica espontânea foi encontrada em 35,3% dos pacientes, sendo mais frequente no sexo feminino, com tempo mais prolongado para controle dos sintomas e maior frequência de urticária colinérgica. Conclusão A confirmação de urticária crônica induzida nos pacientes com suspeita da doença foi elevada. Houve boa resposta ao anti-histamínico. Na concomitância com urticária crônica espontânea, observou-se maior tempo para o controle dos sintomas e maior frequência de urticária colinérgica.

Missed meal boluses contribute to suboptimal glucose control. There has been limited evaluation of missed boluses for complex or high glycemic index meals while on hybrid closed loop AID systems. Ten subjects with type 1 diabetes (50% male), age 52±10 y, A1C 7.1±0.9%, insulin requirement 0.5±0.2 U/kg/day, used the Lilly investigational AID system (model predictive control algorithm) during a 48 h inpatient observation with 6 meals. For each subject, the 2 breakfast (pancake; [60 g carbohydrate (CHO), 15±4 g fat]) and 2 dinner (pizza; [53±3 g CHO, 20±1 g fat]) meals were identical, and were consumed with or without a pre-meal insulin bolus. Lunch meals were subject-selected (44±16 g CHO, 7±5 g fat), and appropriate pre-meal boluses were administered. Time-in-range (TIR, 70-180 mg/dL) overnight was 99.2±9.5% and following the lunches was 82.1±26.4%. In contrast, TIR following pancake and pizza challenges with bolus were 56.0±34.4% and 65.8±29.6%, and without bolus were 17.8±5.1% and 36.5±25.2%, respectively. Incremental area under the curve (0-2 h) following the pancake meal was larger than the pizza meal within both the bolused and non-bolused scenarios (Table). This study highlights the importance of structured, but varied meal challenge tests in the evaluation of AID system performance. Meal macronutrient content affects AID performance in bolused and non-bolused scenarios. Disclosure A. Bartee: None. R.L. Brazg: None. M. Katz: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. A. LaLonde: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. H. Wolpert: Employee; Self; Eli Lilly and Company. R. Jones: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company.

Background Cough is predictive of exacerbations of chronic obstructive pulmonary disease (COPD). Little is known about cough reflex sensitivity during exacerbation of COPD and whether it is associated with exacerbation frequency. This pilot study aimed to investigate cough reflex sensitivity during and following recovery from exacerbation of COPD, and its association with the frequency of future exacerbations. In addition, the repeatability of cough reflex sensitivity in stable COPD was investigated. Methods Twenty participants hospitalised with exacerbation of COPD underwent inhaled capsaicin challenge during exacerbation and after 6 weeks of recovery. The frequency of future exacerbations was monitored for 12 months. The repeatability of cough reflex sensitivity was assessed in separate participants with stable COPD, who underwent 2 capsaicin challenge tests, 6 weeks apart. Results Cough reflex sensitivity was heightened during exacerbation of COPD. Geometric mean (SD) capsaicin concentration thresholds to elicit 5 coughs (C5) during exacerbation and after 6 weeks of recovery were 1.76 (3.73) vs. 8.09 (6.25) μmol L−1, respectively (p ρ = − 0.687, p = 0.003). C5 was highly repeatable over 6 weeks in stable COPD, and intraclass correlation coefficient was 0.85. Conclusion Cough reflex sensitivity is heightened during exacerbation of COPD and reduces after recovery. The persistence of cough reflex hypersensitivity at recovery was associated with the frequency of future exacerbations.

Objectives. To describe clinical manifestations and performed diagnostic workup, focusing drug challenge tests (DCT), in patients with drug allergy. Methods. Retrospective study including all patients with skin tests (STs) or DCT-based drug allergy diagnosis, between 01/2014 - 06/2018 in a Portuguese allergy unit. Data were collected from electronic and paper-based clinical records. Results. We had 75 drug allergy diagnoses. Most index reactions were mild and major or equal 1 hour after drug intake. 59 (78%) diagnoses were based on DCTs, all based on multistep protocols with major or equal 3 predicted steps. Only 10% of the DCT were positive during up-dosing; timing and severity of the index reaction predicted DCT interruption during up-dosing. Conclusions. Most drug allergy diagnoses were based on multistep DCT. The identified predictors of DCT interruption during up-dosing can support the development of more personalized DCTs protocols. info:eu-repo/semantics/publishedVersion

Background Paracetamol, a non-steroidal anti-inflammatory drug, is commonly being used for fever and pain relief worldwide. The aim of this study was to evaluate children with a suspected history of paracetamol hypersensitivity. Methods Sixty patients who were referred to our clinic in between January 2015 and December 2018 with a suspected history of paracetamol hypersensitivity were included. Reactions were classified according to the European Network for Drug Allergy (ENDA)/Global Allergy and Asthma European Network classification and European Academy of Allergy and Clinical Immunology (EAACI)/ENDA Position Paper. Diagnoses were confirmed by skin tests and oral challenge tests (OCTs). In those with verified paracetamol hypersensitivity, an OCT with a strong COX-1 inhibitor was performed to classify the type of the reaction to refer as either selective or cross-intolerance hypersensitivity. A subsequent OCT with a selective COX-2 inhibitor was performed in those cross-intolerant patients to find out a safe alternative drug. Results Sixty OCTs with paracetamol were performed to patients with a median age of 8.5 years, and hypersensitivity to paracetamol was verified in 8 patients. Four children were classified as selective responders, and 3 were classified as cross-intolerant after OCT with a COX-1 inhibitor. Overall, skin test positivity for paracetamol was detected in only one patient, in whom OCT with paracetamol was negative. In all 3 cross-intolerant patients, a safe alternative non-steroidal anti-inflammatory drug was identified after an OCT with a selective COX-2 inhibitor. Conclusion OCT stands as the gold-standard procedure in verifying the diagnosis of patients with paracetamol-induced drug hypersensitivity, as well as, in defining the type of reactions and finding out safe alternative drugs.

Mathematical models were evaluated to predict growth of L. monocytogenes in mould/smear-ripened cheeses with measured dynamic changes in product characteristics and storage conditions. To generate data for model evaluation three challenge tests were performed with mould-ripened cheeses produced by using milk inoculated with L. monocytogenes. Growth of L. monocytogenes and lactic acid bacteria (LAB) in the rind and in the core of cheeses were quantified together with changes in product characteristics over time (temperature, pH, NaCl/aw, lactic- and acetic acid concentrations). The performance of nine available L. monocytogenes growth models was evaluated using growth responses from the present study and from literature together with the determined or reported dynamic product characteristics and storage conditions (46 kinetics). The acceptable simulation zone (ASZ) method was used to assess model performance. A reduced version of the Martinez-Rios et al. (2019) model (https://doi.org/10.3389/fmicb.2019.01510) and the model of Ostergaard et al. (2014) (https://doi.org/10.1016/j.ijfoodmicro.2014.07.012) had acceptable performance with a ASZ-score of 71-70% for L. monocytogenes growth in mould/smear-ripened cheeses. Models from Coroller et al. (2012) (https://doi.org/10.1016/j.ijfoodmicro.2011.09.023) had close to acceptable performance with ASZ-scores of 67-69%. The validated models (Martinez-Rios et al., 2019; Ostergaard et al., 2014) can be used to facilitate the evaluation of time to critical L. monocytogenes growth for mould/smear-ripened cheeses including modification of recipes with for example reduced salt/sodium or to support exposure assessment studies for these cheeses.

Introduction and objectives Occupational causes are thought to account for 20% of the global burden of asthma. The gold standard test for identifying occupational asthma (OA) is specific inhalational challenge to the suspected occupational agent.1 However, a negative SIC does not always exclude a diagnosis of OA. We investigated the reasons why challenge tests may be negative and associated outcomes from two UK centres. Methods We performed a retrospective review of the outcomes of 79 consecutive negative SICs carried out between 2008 and 2019 in North Manchester General Hospital (NMGH) and Birmingham Heartlands Hospital (BHH). Repeat negative SICs for the same patient were also included. Demographic data, serial peak flow analysis, occupation, current exposures, and progress post SIC were reviewed. Patients were followed up post SIC and further testing (either repeat SIC or other) were performed if ongoing symptoms were present. Results Of the79 negative SICs reviewed, 23 were at NMGH and 56 at BHH. Thirty-six workers (45%) were female, median age 51 years (IQR 41–55.5). Ten workers (13%) had a history of previous asthma. Sixty five percent of SICs had an OASYS score of ≥2.51 i.e. positive for work effect prior to testing. Of the 79 SICs carried out, 50 were subsequently diagnosed with occupational asthma with diagnostic serial PEF records and/or repeat testing. The most common reason for a negative SIC was testing to the wrong agent (figure 1). Conclusions This data suggests that there is a high rate of negative SICs in patients who have a diagnosis of occupational asthma, which is mainly due to exposures to the wrong agent in the SIC. It is crucial that patients are followed up post negative SIC and re investigated early if experiencing ongoing symptoms. Reference Specific inhalation challenge in the diagnosis of occupational asthma: consensus statemen Vandenplas O. et al. European Respiratory Journal 2014 43: 1573–1587.

Chicken meats are considered as main sources associated with Salmonella infections in humans. In this study, lytic phages against Salmonella were isolated and examined for their efficacy to control Salmonella. Eighteen lytic phages were isolated from raw chicken skin and gizzard. Five phages belonging to Myoviridae and Siphoviridae families were characterized and selected for bacterial challenge tests. The treatment of raw chicken breast samples contaminated with S. Enteritidis and S. Typhimurium at 8 °C by the cocktail of five phages significantly reduced (P

In this study Brain Heart Infusion broth inoculated with Listeria monocytogenes with a concentration of acetic acid of 24.98 mM or a concentration of 44.40 mM of lactic acid did not determine the increase in absorbance in 7 days. A concentration of acetic acid of 24.98 mM and a concentration of 22.20 mM of lactic acid were effective against Bacillus cereus growth. Then, challenge tests on primo sale cheese were conducted to establish if these concentrations were efficient when applied to cheese. After inoculum with the pathogens (2 log CFU g−1), cheese was dipped with acetic and lactic acid solutions. In a first trial, L. monocytogenes inoculated, showed the absence of significant differences in growth at 4 °C among the treated series (Ac1: acetic acid - 49.96 mM; Ac2: 24.98 mM; Lac1: lactic acid – 88.80 mM; Lac2: 44.40 mM) if compared to Control (CTRL) series (dipped with sterile water). At 8 °C, a significantly lower growth in Ac1 samples if compared to control ones and to all the treated series was observed (P

A bronchial allergen challenge may serve both as a diagnostic as well as investigative procedure. Its usage in the diagnosis of asthma is infrequent due to its time-consuming nature as well as (in our opinion) an unfounded fear for a patient's safety. It is quite useful in the diagnostics of workplace related illnesses. Due to its ability to produce a controlled, long-lasting allergic-inflammatory reaction in the bronchi, this procedure is commonly used in research settings as well as in the assessment of new substances which may potentially have a place in the treatment of asthma, for ex. through the blocking of late asthmatic reactions. Changes stimulated by a bronchial allergen challenge may be evaluated by many methods using different materials, i.e. samples obtained from direct biopsies, bronchoalveolar lavages, exhaled breath condensates, or measured fractional exhaled nitric oxide. This procedure is a seemingly ideal research and diagnostic tool, however, a common protocol for its execution has not yet been accepted. Recent legal regulations have resulted in difficulties obtaining various allergens for challenge tests. Hopefully this is a temporary and minor setback for this very useful and constantly developing procedure.

The aim of this study was to quantify the influence of temperature on pH min -values of Listeria monocytogenes as used in cardinal parameter growth models and thereby improve the prediction of growth for this pathogen in food with low pH. Experimental data for L. monocytogenes growth in broth at different pH-values and at different constant temperatures were generated and used to determined pH min -values. Additionally, pH min -values for L. monocytogenes available from literature were collected. A new pH min -function was developed to describe the effect of temperatures on pH min -values obtained experimentally and from literature data. A growth and growth boundary model was developed by substituting the constant pH min -value present in the Mejlholm and Dalgaard (2009) model (J. Food. Prot. 72, 2132-2143) by the new pH min -function. To obtain data for low pH food, challenge tests were performed with L. monocytogenes in commercial and laboratory-produced chemically acidified cheese including glucono-delta-lactone (GDL) and in commercial cream cheese. Furthermore, literature data for growth of L. monocytogenes in products with or without GDL were collected. Evaluation of the new and expanded model by comparison of observed and predicted μ max -values resulted in a bias factor of 1.01 and an accuracy factor of 1.48 for a total of 1,129 growth responses from challenge tests and literature data. Growth and no-growth responses of L. monocytogenes in seafood, meat, non-fermented dairy products, and fermented cream cheese were 90.3% correctly predicted with incorrect predictions being 5.3% fail-safe and 4.4% fail-dangerous. The new pH min -function markedly extended the range of applicability of the Mejlholm and Dalgaard (2009) model from pH 5.4 to pH 4.6 and therefore the model can now support product development, reformulation or risk assessment of food with low pH including chemically acidified cheese and cream cheese.

In the present work, a combined hurdle approach for fermented meat preservation was investigated. Challenge tests were performed in Chorizo sausage model using the maximum allowed NaNO2 amount (150 mg/kg), a reduced amount (75 mg/kg) and no nitrite, with and without protective cultures inoculation. Cocktail strains of L. monocytogenes and Salmonella spp. were used as indicator strains. In a nitrite reduced sausage model, L. monocytogenes growing trend did not significantly change (p > 0.05) when compared with that containing higher nitrite concentration (150 mg/kg NaNO2). The addition of L. plantarum PSC20 significantly lowered L. monocytogenes growth when compared with control batches without PCS20 (p < 0.05), obtaining 3.84 log cfu/g and 2.62 log cfu/g lower counts in the batches with 150 mg/kg NaNO2 and 75 mg/kg NaNO2 respectively. None of the protective cultures demonstrated in situ antagonistic activity against Salmonella spp. This work pointed out that the reduction of nitrites with the combined use of a protective culture could be a feasible approach to control L. monocytogenes growth in fermented meat foods.

This study involved ten enterprises producing Italian salami, 20 different samples of fermented sausages underwent challenge tests to assess and record the following parameters: time, temperature, pH, aw, and Salmonella counts. A linear regression model was used to describe the Salmonella spp. decay: at the end of the process the result of total Salmonella reduction was 0.97–5.84 Log10 CFU/g and it was significantly associated with pH at the end of acidification/drying process, aw at the end of seasoning period, the duration of seasoning, and the caliber of salami respectively. High Pressure Processing (HPP) further reduced the Salmonella level by 2.41–5.84 Log10 CFU/g with an efficacy that resulted inversely associated with aw of salami at the end of seasoning; the objective of 5-Log reduction was always reached in all the cases tested by the production process plus HPP. This model could be a useful tool for enterprises and Authorities to evaluate the efficacy of the processes to reduce Salmonella load for exportation to the U.S.

Metabolic challenge tests may be a valuable tool to magnify the effects of diet on health. The use of transcriptomics enables a more extensive characterization of the effects of diet. The question remains whether transcriptome time-course analyses during challenge tests will deliver more information on the effect of diet than a static fasting measurement. A dietary intervention known to improve health is energy restriction (ER). Seventy-two healthy, overweight men and women aged 50-65 were subjected to an oral glucose tolerance test (OGTT) and a mixed-meal test (MMT) before and after 12 wk of a 20% ER diet or control diet. Whole-genome gene expression of peripheral blood mononuclear cells was performed before and after the intervention. This was done during fasting, during the OGTT at 30, 60, and 120 min, and during the MMT at 60, 120, 240, and 360 min. Upon ER, the OGTT resulted in a faster and more pronounced down-regulation in gene expression of oxidative phosphorylation, cell adhesion, and DNA replication compared with the control. The MMT showed less-consistent effects. The OGTT combined with transcriptomics can be used to measure dynamic cellular adaptation upon an intervention that cannot be determined with a static fasting measurement.-Van Bussel, I. P. G., Fazelzadeh, P., Frost, G. S., Rundle, M., Afman, L. A. Measuring phenotypic flexibility by transcriptome time-course analyses during challenge tests before and after energy restriction.

Background Specific challenge tests (SIC) are regarded as the reference standard in the diagnosis of occupational asthma. As part of an audit of specific inhalation testing 2006–2015 we have identified 12 workers whose SIC were negative but for which there was strong alternative evidence of occupational asthma. We have looked for causes for the discordance. Methods We performed SIC in 125/343 workers with possible occupational asthma with latency referred to us from 2006–2015. In 72 the SIC was negative, 12 of these had serial PEF evidence of occupational asthma with positive scores from the Oasys computer assisted diagnostic program both for the Area-Between Curves (ABC)>15 litres/min/hour and discriminant analysis (Oasys score)>2.5 (combined specificity 100%, sensitivity 60% with positive SIC as positive referent and non-exposed asthmatics as negative referent), and both scores becoming negative after relocation with the same employer. It is likely that at least these 12 had falsely negative SICs. We have investigated why the SICs may have been negative following a subjective review of all data. Results The mean ABC score was 30.3 l/min/hour (range 60.8–19.1) pre-relocation and −12.1 l/min/hour (range −48.6 -+9.9) post-relocation. The Oasys discriminant scores were 3.52 (4–2.67) pre-relocation and 1.73 (2.29–1.13) post-relocation. The cause was likely to be an agent not tested in SIC despite testing 4–8 agents each in 7 workers. Likely missed causes included a mouldy school building (figure 1), environmental welding fume, cleaning materials and a lack of protein source for chlorine-releasing agents. In 2 there was no exposure to the likely cause for >6 months, in 3 the control days were too unstable to identify late reactions, perhaps related to LABA withdrawal pre-challenge, and in 3 the work-exposures were likely to be much higher than used in the SIC (MDI, shrink-wrap and plastic moulding) (>1 reason possible). 9 were taking ICS during SIC which may have limited reactions. Conclusion Occupational asthma is still possible despite negative SIC. The figure shows the mean hourly PEF on days at home and days at work in a DT technician before (top) and after (bottom) relocating to new buildings with the same work exposures.

This review incorporates findings from studies of oral food challenges (OFC) over the last decade and highlights the latest innovations and understanding of the procedure. PRACTALL guidelines are widely used in OFC research, but there is still no international consensus on the OFC protocol in clinical practice. Guidelines for performing OFC in clinical practice have been updated to include oral food challenges for infants. There have been advances in predictive models for outcomes and severity of reaction during OFC that take into account multiple clinical data as well as newer laboratory modalities. Low-dose OFC and eliciting threshold dose determination are being examined for additional diagnostic and therapeutic use in the management of food allergy. Quality-of-life considerations have also been reviewed, as well as post-OFC assessment and care. The OFC remains an important diagnostic tool in the management of food allergy and in clinical research. Advances in the field should improve safety and broaden the clinical applications of this essential procedure.

A model describing Listeria innocua evolution according to process parameters of 51 Italian salami processes and HPP in 31 companies was developed. A total of 51 challenge tests were performed. During processing a L. innocua reduction of 0.34–4.32 Log10 CFU/g was observed and HPP further reduced the count of 0.48–3.47 Log10 CFU/g; an overall reduction of 1.04–5.68 is reached. PH after acidification/drying process, aw after seasoning, duration of the seasoning and caliber resulted associated (p < 0.05) with L. innocua decrease. HPP efficacy was associated (p < 0.05) with aw and pH of the product: higher the pH and aw after the acidification/drying and seasoning phases, higher resulted the L. innocua reduction after HPP. No significant association was observed between L. innocua and salt, nitrate and starter content and other characteristics of process. The model meets companies and Authorities needs and represents a useful tool to predict L. monocytogenes lethality, giving recommendations to food business operators interested in exportation to the U.S.

Cheese potentially allowing the growth of Listeria monocytogenes must be free of the pathogen in 25 g before being put on the market, while 100 cfu/g is tolerated when the pathogen is unable to grow. Challenge tests were performed in order to assess the growth potential of L. monocytogenes in at least one batch of 32 Belgian cheese varieties from 32 factories. All varieties were grouped in four categories: unripened acid-curd cheeses, mold-ripened soft cheeses, smear-ripened soft cheeses and ripened semi-hard cheeses. Associated microflora and cheese physicochemical characteristics were also studied. A cocktail of three strains was used to inoculate cheese on the first day of shelf-life, and samples were stored until the end of shelf-life at 7–9 °C. Growth potential was considered as the difference (a) between median contamination at the end and at the beginning of the test or (b) between the highest value at the end of the test and the lowest value at its beginning. L. monocytogenes always decreased in unripened acid-curd cheeses but showed extended growth in 21 out of 25 batches of ripened soft cheese. Contrasting results were obtained for semi-hard cheeses, as important intra- and inter-batch variability was observed. For the latter, the recommended method based on medians to calculate the growth potential led to erroneous food safety considerations, and it should always be advised to focus on absolute levels.

Optical rhinometry is the only diagnostic tool in rhinitis for assessing real-time changes in nasal occlusion. It illustrates lumen changes of nasal mucosa vessels in response nonspecific/specific factors and not only. The first attempts to standardize the method conducted by German researchers show the potential of optical rhinometry not only as regards challenge tests, but also vice versa, in respect of the anemization of the mucosa it evaluates the extent of the oedema which occurred in the pathomechanism of non-allergic rhinitis. The relatively small number of publications in the domain of interest demonstrates there is a need to conduct further research on the suitability of the above-mentioned technique for the evaluation of nasal patency in the field of rhinological diagnostics.

International audience; Ruminants are healthy carriers of Shiga toxin producing Escherichia, coli (STEC). If good hygienic and agricultural practices at the farm level, especially during the milking process, are not adequately followed, milk and dairy products made with raw milk could become contaminated. Sporadic cases and rare food outbreaks have been linked with dairy products. Consequently, understanding STEC behavior in cheeses would help to evaluate risks for human health. The behavior of 4 different STEC strains belonging to the serotypes O26:H11, O103:H2, O145:H28, and O157:H7 were monitored during the manufacture, ripening, and storage of a white mold soft cheese. These strains, originating from dairy products, were inoculated individually in raw milk from cow at 102 cfu/mL. During the first 24 to 30 h of the manufacturing stage, the STEC level increased by 2 to 3 log(10) cfu/g. Over the course of the ripening stage, the concentration of the non-O157 STEC remained relatively constant, whereas a decrease of the E. coli, O157:H7 concentration was observed. During the storage stage, the level of the different non O157 STEC strains decreased slowly in the core and in the rind of cheeses. The non-O157 STEC level reached between 3.1 and 4.1 log(10) cfu/g at d 56. Interestingly, the concentration of the E. coli O157:H7 strain decreased dramatically: the strains remained detectable only after enrichment. During ripening and storage, STEC levels were generally higher in rinds than in cheese cores. In contrast to what was seen in cheese cores, the E. coli O157:H7 strain remained enumerable in rinds during these steps. These results highlight that STEC can grow during the manufacture and survive during the ripening and storage of a white mold soft cheese.

Raw minimally processed vegetables and fruits as well as boiled pasta and potato are the main ingredients of ready-to-eat (RTE) salads. These ingredients are diverse in their ability to support growth of Listeria monocytogenes . The objective of this study was to determine to what extent different ingredients can contribute to growth of L. monocytogenes in RTE salads. This was done by assessing the growth capacity of L. monocytogenes in ingredients of RTE salads by means of challenge tests and determination of the effect of product characteristics and presence of competitive flora. The majority of the tested products did not support or hardly supported growth of L. monocytogenes . The calculated maximum increase of 3.4 log CFU/g was exceeded in Galia melon, potato and pasta products. In RTE dinner salads, growth of L. monocytogenes was supported by the carbohydrate component. Galia melon, which is often used as ingredient of fruit salads, can contribute to growth of L. monocytogenes in these products. Growth inhibition, or differences in relative increase, could not always be explained by a w , pH or presence of competitive flora. The effect of competitive flora, especially lactic acid bacteria, on growth inhibition was observed in non-pasteurized potato, white cabbage and mango.

Background Soybeans are one of causative foods for infantile onset allergies in Japan. This study aimed to analyze the results of soybean challenge tests that were conducted over approximately 7 years at our institution. Using the test data, we sought to identify the responses and clinical profiles of patients with soybean allergies, and to investigate the relationship between the responses and soybean sensitization status. Methods Between July 2004 and May 2010, 142 cases (125 patients) underwent food challenge tests (100 g of silken tofu) for the diagnosis of soybean allergy or confirmation of their tolerance. The patients' characteristics, soybean sensitization status, and responses to the challenge tests were retrospectively evaluated. Results Among the subjects who underwent the soybean challenge test, the male/female ratio was 1.6 (87/55), and the mean age at the test was 2.8 ± 1.7 years. The positive rate for the challenge test was 38.7%. Induced symptoms were observed in the skin (81.8%), respiratory system (50.9%), and gastrointestinal system/mucosal membrane/anaphylaxis (12.7%). Intramuscular epinephrine was administered to all 7 patients who experienced an anaphylactic reaction. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic efficiency of soybean-specific IgE titers were low for predicting the responses to the challenge test. Conclusions Soybean allergies were diagnosed in only 18% of the subjects with positive sensitization to soybeans. Therefore, soybean-specific IgE titers are not an effective predictor of a positive response to the challenge test.