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1. Discrimination training affects stimulus generalization in mice during Pavlovian eyeblink conditioning

Author

Fiocchi, Francesca Romana, van Dorp, Nikki E S, Dijkhuizen, Stephanie, van den Berg, Maurits, Wong, Aaron, De Zeeuw, Chris I, Boele, Henk-Jan, Fiocchi, Francesca Romana, van Dorp, Nikki E S, Dijkhuizen, Stephanie, van den Berg, Maurits, Wong, Aaron, De Zeeuw, Chris I, and Boele, Henk-Jan

Abstract

The delicate balance between discrimination and generalization of responses is crucial for survival in our ever-changing environment. In particular, it is important to understand how stimulus discrimination affects the level of stimulus generalization. For example, when we use non-differential training for Pavlovian eyeblink conditioning to investigate generalization of cerebellar-related eyelid motor responses, we find generalization effects on amount, amplitude and timing of the conditioned responses. However, it is unknown what the generalization effects are following differential training. We trained mice to close their eyelids to a 10 kHz tone with an air-puff as the reinforcing stimulus (CS+), while alternatingly exposing them to a tone frequency of either 4 kHz, 9 kHz or 9.5 kHz without the air-puff (CS-) during the training blocks. We tested the generalization effects during the expression of the responses after the training period with tones ranging from 2 kHz to 20 kHz. Our results show that the level of generalization tended to positively correlate with the difference between the CS+ and the CS- training stimuli. These effects of generalization were found for the probability, amplitude but not for the timing of the conditioned eyelid responses. These data indicate the specificity of the generalization effects following differential versus non-differential training, highlighting the relevance of discrimination learning for stimulus generalization.

Published
2024

2. Long term optical variability of two HMXB

Author

Nesci, Roberto, Fiocchi, Mariateresa, Vagnozzi, Antonio, Nesci, Roberto, Fiocchi, Mariateresa, and Vagnozzi, Antonio

Abstract

We discuss the optical light curves of two Be X-ray Binaries, IGR J06074+2205 and SAX J2103.5+4545 recovered from the ATLAS, ZTF and ASAS-SN databases. Both sources show long term optical variability of 620 and 420 days respectively, with color redder when brighter. We suggest that this is due to the precession of the circumstellar disk. Another possibility is the propagation of a density wave in the disk. We remark that only these two sources show a large amplitude, periodic optical variability out of a sample of 16 well studied High Mass X-ray Binaries (HMXB) with a Main Sequence primary star., Comment: 9 pages, 7 figures, accepted for OEJV March 2024

Published
2024
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3. The challenge of identifying INTEGRAL sources on the Galactic plane

Author

Landi, Raffaella, Bassani, Loredana, Bruni, Gabriele, Molina, Manuela, Masetti, Nicola, Malizia, Angela, Fiocchi, Mariateresa, Bazzano, Angela, Ubertini, Pietro, Landi, Raffaella, Bassani, Loredana, Bruni, Gabriele, Molina, Manuela, Masetti, Nicola, Malizia, Angela, Fiocchi, Mariateresa, Bazzano, Angela, and Ubertini, Pietro

Abstract

The International Gamma-ray Astrophysics Laboratory (INTEGRAL) has been surveying the sky above 20 keV since its launch in 2002 providing new insights into the nature of the sources that populate our Universe at soft gamma-ray energies. The latest IBIS/ISGRI survey lists 929 hard X-ray sources, of which 113 are reported as unidentified, i.e. lacking a lower energy counterpart or simply not studied in other wavebands. To overcome this lack of information, we either browsed the X-ray archives, or, if no data in the X-ray band were available, we requested Target of Opportunity (ToO) observations with the X-ray Telescope (XRT) on-board the Neil Gehrels Swift Observatory. Following this approach, we selected a sample of 10 objects for which X-ray data were key to investigate their nature. We found a single X-ray association for all of the sources, except for IGR J16267-3303, for which two X-ray detections were spotted within the IBIS positional uncertainty. We then browsed multi-waveband archives to search for counterparts to these X-ray detections at other wavelengths and analysed X-ray spectral properties to determine their nature and association with the high-energy emitter. As a result of our analysis, we identified the most likely counterpart for 7 sources, although in some cases its nature/class could not be definitely assessed on the basis of the information collected. Interestingly, SWIFT J2221.6+5952, first reported in the 105-month Swift/Burst Alert Telescope (BAT) survey, is the only source of the sample for which we did not find any counterpart at radio/optical/IR wavebands. Finally, we found that two IBIS source, IGR J17449-3037 and IGR J17596-2315 are positionally associated with a Fermi Large Area Telescope (LAT) object., Comment: 13 figures, 6 tables. Accepted for publication in the Journal of High Energy Astrophysics

Published
2024

4. Quadri regionali. Lombardia, in Archeologia cristiana in Italia, ricerche, metodi e prospettive (1993-2022

Author

BRACONI M., DAVID M., FIOCCHI NICOLAI V., NUZZO D., SPERA L., STASOLLA F.R., Sannazaro, Marco, Sannazaro (ORCID:0000-0001-6628-7911), BRACONI M., DAVID M., FIOCCHI NICOLAI V., NUZZO D., SPERA L., STASOLLA F.R., Sannazaro, Marco, and Sannazaro (ORCID:0000-0001-6628-7911)

Abstract

The investigations of Christian archaeology over the last thirty years in Lombardy have contributed to a great deal of knowledge about early Christian Milan and other ancient cities in the region as a result of new excavations, but also thanks to the reconsideration of material from older investigations. There has also been much activity in the rural area with the recognition of many early Christian and early medieval cult buildings.

Published
2024

5. Lacerti di strutture e affreschi paleocristiani nel cimitero ad martyres di Milano

Author

BRACONI M., DAVID M., FIOCCHI NICOLAI V., NUZZO D., SPERA L., STASOLLA F.R., Sannazaro, Marco, Fedeli, A. M., Pagani, Carla, SANNAZARO M. (ORCID:0000-0001-6628-7911), BRACONI M., DAVID M., FIOCCHI NICOLAI V., NUZZO D., SPERA L., STASOLLA F.R., Sannazaro, Marco, Fedeli, A. M., Pagani, Carla, and SANNAZARO M. (ORCID:0000-0001-6628-7911)

Abstract

Emergency excavations in Via S. Valeria in Milan uncovered the remains of an early Christian mausoleum that preserved both in situ and in the collapse deposits the remains of a figurative pictorial cycle that can be dated to the second half of the 4th century.

Published
2024

6. Recommendations for asthma monitoring in children:A PeARL document endorsed by APAPARI, EAACI, INTERASMA, REG, and WAO

Author

Papadopoulos, Nikolaos G., Custovic, Adnan, Deschildre, Antoine, Gern, James E., Nieto Garcia, Antonio, Miligkos, Michael, Phipatanakul, Wanda, Wong, Gary, Xepapadaki, Paraskevi, Agache, Ioana, Arasi, Stefania, Awad El-Sayed, Zeinab, Bacharier, Leonard B., Bonini, Matteo, Braido, Fulvio, Caimmi, Davide, Castro-Rodriguez, Jose A., Chen, Zhimin, Clausen, Michael, Craig, Timothy, Diamant, Zuzana, Ducharme, Francine M., Ebisawa, Motohiro, Eigenmann, Philippe, Feleszko, Wojciech, Fierro, Vincezo, Fiocchi, Alessandro, Garcia-Marcos, Luis, Goh, Anne, Gómez, René Maximiliano, Gotua, Maia, Hamelmann, Eckard, Hedlin, Gunilla, Hossny, Elham M., Ispayeva, Zhanat, Jackson, Daniel J., Jartti, Tuomas, Jeseňák, Miloš, Kalayci, Omer, Kaplan, Alan, Konradsen, Jon R., Kuna, Piotr, Lau, Susanne, Le Souef, Peter, Lemanske, Robert F., Levin, Michael, Makela, Mika J., Mathioudakis, Alexander G., Mazulov, Oleksandr, Morais-Almeida, Mário, Murray, Clare, Nagaraju, Karthik, Novak, Zoltan, Pawankar, Ruby, Pijnenburg, Marielle W., Pite, Helena, Pitrez, Paulo M., Pohunek, Petr, Price, David, Priftanji, Alfred, Ramiconi, Valeria, Rivero Yeverino, Daniela, Roberts, Graham, Sheikh, Aziz, Shen, Kun Ling, Szepfalusi, Zsolt, Tsiligianni, Ioanna, Turkalj, Mirjana, Turner, Steve, Umanets, Tetiana, Valiulis, Arunas, Vijveberg, Susanne, Wang, Jiu Yao, Winders, Tonya, Yon, Dong Keon, Yusuf, Osman M., Zar, Heather J., Papadopoulos, Nikolaos G., Custovic, Adnan, Deschildre, Antoine, Gern, James E., Nieto Garcia, Antonio, Miligkos, Michael, Phipatanakul, Wanda, Wong, Gary, Xepapadaki, Paraskevi, Agache, Ioana, Arasi, Stefania, Awad El-Sayed, Zeinab, Bacharier, Leonard B., Bonini, Matteo, Braido, Fulvio, Caimmi, Davide, Castro-Rodriguez, Jose A., Chen, Zhimin, Clausen, Michael, Craig, Timothy, Diamant, Zuzana, Ducharme, Francine M., Ebisawa, Motohiro, Eigenmann, Philippe, Feleszko, Wojciech, Fierro, Vincezo, Fiocchi, Alessandro, Garcia-Marcos, Luis, Goh, Anne, Gómez, René Maximiliano, Gotua, Maia, Hamelmann, Eckard, Hedlin, Gunilla, Hossny, Elham M., Ispayeva, Zhanat, Jackson, Daniel J., Jartti, Tuomas, Jeseňák, Miloš, Kalayci, Omer, Kaplan, Alan, Konradsen, Jon R., Kuna, Piotr, Lau, Susanne, Le Souef, Peter, Lemanske, Robert F., Levin, Michael, Makela, Mika J., Mathioudakis, Alexander G., Mazulov, Oleksandr, Morais-Almeida, Mário, Murray, Clare, Nagaraju, Karthik, Novak, Zoltan, Pawankar, Ruby, Pijnenburg, Marielle W., Pite, Helena, Pitrez, Paulo M., Pohunek, Petr, Price, David, Priftanji, Alfred, Ramiconi, Valeria, Rivero Yeverino, Daniela, Roberts, Graham, Sheikh, Aziz, Shen, Kun Ling, Szepfalusi, Zsolt, Tsiligianni, Ioanna, Turkalj, Mirjana, Turner, Steve, Umanets, Tetiana, Valiulis, Arunas, Vijveberg, Susanne, Wang, Jiu Yao, Winders, Tonya, Yon, Dong Keon, Yusuf, Osman M., and Zar, Heather J.

Abstract

Monitoring is a major component of asthma management in children. Regular monitoring allows for diagnosis confirmation, treatment optimization, and natural history review. Numerous factors that may affect disease activity and patient well-being need to be monitored: response and adherence to treatment, disease control, disease progression, comorbidities, quality of life, medication side-effects, allergen and irritant exposures, diet and more. However, the prioritization of such factors and the selection of relevant assessment tools is an unmet need. Furthermore, rapidly developing technologies promise new opportunities for closer, or even “real-time,” monitoring between visits. Following an approach that included needs assessment, evidence appraisal, and Delphi consensus, the PeARL Think Tank, in collaboration with major international professional and patient organizations, has developed a set of 24 recommendations on pediatric asthma monitoring, to support healthcare professionals in decision-making and care pathway design. (Figure presented.).

Published
2024

7. In Vitro Assessment of the Neuro-Compatibility of Fe-20Mn as a Potential Bioresorbable Material for Craniofacial Surgery

Author

Ajami, Sara, Kraaneveld, Charlotte, Koudstaal, Maarten, Dunaway, David, Jeelani, Noor Ul Owase, Schievano, Silvia, Bregoli, Chiara, Fiocchi, Jacopo, Biffi, Carlo Alberto, Tuissi, Ausonio, Borghi, Alessandro, Ajami, Sara, Kraaneveld, Charlotte, Koudstaal, Maarten, Dunaway, David, Jeelani, Noor Ul Owase, Schievano, Silvia, Bregoli, Chiara, Fiocchi, Jacopo, Biffi, Carlo Alberto, Tuissi, Ausonio, and Borghi, Alessandro

Abstract

Background and Objectives:Spring-assisted surgery is a popular option for the treatment of non-syndromic craniosynostosis. The main drawback of this procedure is the need for a second surgery for spring removal, which could be avoided if a distractor material could be metabolised over time. Iron–Manganese alloys (FeMn) have a good trade-off between degradation rate and strength; however, their biocompatibility is still debated. Materials and Methods: In this study, the neuro-compatibility of Fe-20Mn (wt.%) was assessed using standard assays. PC-12 cells were exposed to Fe-20Mn (wt.%) and stainless steel via indirect contact. To examine the cytotoxicity, a Cell Tox Green assay was carried out after 1, 2, and 3 days of incubation. Following differentiation, a neurite morphological examination after 1 and 7 days of incubation time was carried out. The degradation response in modified Hank’s solution at 1, 3, and 7 days was investigated, too. Results: The cytotoxicity assay showed a higher toxicity of Fe-20Mn than stainless steel at earlier time points; however, at the latest time point, no differences were found. Neurite morphology was similar for cells exposed to Fe-20Mn and stainless steel.Conclusions: In conclusion, the Fe-20Mn alloy shows promising neuro-compatibility. Future studies will focus on in vivo studies to confirm the cellular response to Fe-20Mn.

Published
2024

8. Impact of Exacerbation History on Dupilumab Efficacy in Children with Uncontrolled Moderate-to-Severe Asthma: LIBERTY ASTHMA VOYAGE Study

Author

Guilbert,Theresa W, Tolcachier,Alberto, Fiocchi,Alessandro G, Katelaris,Constance, Phipatanakul,Wanda, Begin,Philippe, de Mir,Inés, Altincatal,Arman, Gall,Rebecca, Ledanois,Olivier, Radwan,Amr, Jacob-Nara,Juby A, Deniz,Yamo, Rowe,Paul J, Guilbert,Theresa W, Tolcachier,Alberto, Fiocchi,Alessandro G, Katelaris,Constance, Phipatanakul,Wanda, Begin,Philippe, de Mir,Inés, Altincatal,Arman, Gall,Rebecca, Ledanois,Olivier, Radwan,Amr, Jacob-Nara,Juby A, Deniz,Yamo, and Rowe,Paul J

Abstract

Theresa W Guilbert,1 Alberto Tolcachier,2 Alessandro G Fiocchi,3 Constance H Katelaris,4,5 Wanda Phipatanakul,6,7 Philippe Begin,8 Inés de Mir,9 Arman Altincatal,10 Rebecca Gall,11 Olivier Ledanois,12 Amr Radwan,11 Juby A Jacob-Nara,13 Yamo Deniz,11 Paul J Rowe13 1Department of Pediatrics, Cincinnati Children’s Hospital and University of Cincinnati, Cincinnati, OH, USA; 2Center for Allergy and Respiratory Diseases, Buenos Aires, Argentina; 3Bambino Gesù Children’s Hospital IRCCS, Rome, Italy; 4Department of Medicine, Campbelltown Hospital, Campbelltown, NSW, Australia; 5Immunology & Allergy Unit, Western Sydney University, Sydney, NSW, Australia; 6Department of Allergy and Immunology, Boston Children’s Hospital, Boston, MA, USA; 7Department of Pediatrics, Harvard Medical School, Boston, MA, USA; 8Centre Hospitalier Universitaire (CHU) Sainte-Justine, Montreal, QC, Canada; 9Pediatric Pulmonary Unit, Hospital Universitari Vall d’Hebron, Barcelona, Spain; 10Sanofi, Cambridge, MA, USA; 11Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA; 12Sanofi, Paris, France; 13Sanofi, Bridgewater, NJ, USACorrespondence: Theresa W Guilbert, Cincinnati Children’s Hospital and University of Cincinnati, 3333 Burnet Ave, Cincinnati, OH, 45229, USA, Tel +1 513-636-6771, Email theresa.guilbert@cchmc.orgPurpose: Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukins-4/-13, key and central drivers of type 2 inflammation in multiple diseases. This post hoc analysis of the Phase 3 LIBERTY ASTHMA VOYAGE study (NCT02948959) evaluated the efficacy of dupilumab in children aged 6 to 11 years with moderate-to-severe asthma with a type 2 inflammatory phenotype (blood eosinophil count ≥ 150 cells/μL or fractional exhaled nitric oxide [FeNO] ≥ 20 ppb) and a history of 1, 2, or ≥ 3 prior exacerbations. The impact of baseline type 2 biomarker levels on the efficacy of dupilumab in this population was also investigated.Patients and Meth

Published
2024

9. Impact of Lung Function on Asthma Exacerbation Rates in Children Treated with Dupilumab: The VOYAGE Study

Author

Guilbert,Theresa W, Murphy,Kevin R, Hamelmann,Eckard, Ross,Kristie R, Gupta,Atul, Fiocchi,Alessandro, Xia,Changming, Gall,Rebecca, Ledanois,Olivier, Radwan,Amr, Jacob-Nara,Juby A, Rowe,Paul J, Deniz,Yamo, Guilbert,Theresa W, Murphy,Kevin R, Hamelmann,Eckard, Ross,Kristie R, Gupta,Atul, Fiocchi,Alessandro, Xia,Changming, Gall,Rebecca, Ledanois,Olivier, Radwan,Amr, Jacob-Nara,Juby A, Rowe,Paul J, and Deniz,Yamo

Abstract

Theresa W Guilbert,1 Kevin R Murphy,2 Eckard Hamelmann,3 Kristie R Ross,4 Atul Gupta,5 Alessandro Fiocchi,6 Changming Xia,7 Rebecca Gall,7 Olivier Ledanois,8 Amr Radwan,7 Juby A Jacob-Nara,9 Paul J Rowe,9 Yamo Deniz7 1Cincinnati Children’s Hospital and University of Cincinnati, Cincinnati, OH, USA; 2Boys Town National Research Hospital, Omaha, NE, USA; 3Department of Pediatrics, Children’s Center Bethel, University of Bielefeld, Bielefeld, Germany; 4UH Rainbow Babies and Children’s Hospital, Cleveland, OH, USA; 5King’s College Hospital, London, UK; 6Bambino Gesù Children’s Hospital IRCCS, Rome, Italy; 7Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA; 8Sanofi, Paris, France; 9Sanofi, Bridgewater, NJ, USACorrespondence: Theresa W Guilbert, Cincinnati Children’s Hospital and University of Cincinnati, Cincinnati, OH, USA, Tel +1 513-636-6771, Email theresa.guilbert@cchmc.orgBackground: Severe, uncontrolled asthma and asthma exacerbations in children are associated with abnormal lung function and airway development, and increased risk of chronic obstructive lung disease in adulthood. The rationale for this post hoc analysis was to explore the relationship between changes in asthma exacerbation rates and lung function in children treated with dupilumab.Methods: This post hoc analysis included children aged 6 to 11 years with uncontrolled, moderate-to-severe type 2 asthma (blood eosinophils ≥ 150 cells/μL or fractional exhaled nitric oxide ≥ 20 ppb) who received dupilumab or placebo in the phase 3 LIBERTY ASTHMA VOYAGE study (NCT02948959). Endpoints were the proportion of patients achieving clinically meaningful improvements (≥ 5% or ≥ 10%) in pre-bronchodilator percent-predicted forced expiratory volume in 1 second (ppFEV1) by Week 12, annualized severe asthma exacerbation rates from Week 12– 52, and mean change from baseline in ppFEV1 to Week 12.Results: At Week 12 of VOYAGE, 141/236 (60%) of children treated with dupilumab and 57/114 (50%) of

Published
2024

10. Probabilistic Multi-Layer Perceptrons for Wind Farm Condition Monitoring

Author

Fiocchi, Filippo, Ladopoulou, Domna, Dellaportas, Petros, Fiocchi, Filippo, Ladopoulou, Domna, and Dellaportas, Petros

Abstract

We provide a condition monitoring system for wind farms, based on normal behaviour modelling using a probabilistic multi-layer perceptron with transfer learning via fine-tuning. The model predicts the output power of the wind turbine under normal behaviour based on features retrieved from supervisory control and data acquisition (SCADA) systems. Its advantages are that (i) it can be trained with SCADA data of at least a few years, (ii) it can incorporate all SCADA data of all wind turbines in a wind farm as features, (iii) it assumes that the output power follows a normal density with heteroscedastic variance and (iv) it can predict the output of one wind turbine by borrowing strength from the data of all other wind turbines in a farm. Probabilistic guidelines for condition monitoring are given via a CUSUM control chart. We illustrate the performance of our model in a real SCADA data example which provides evidence that it outperforms other probabilistic prediction models., Comment: 9 pages, 8 figures, 2 tables

Published
2024

11. Introduction

Author

Fiocchi Malaspina, Elisabetta, Silvestrini, Gabriella, Fiocchi Malaspina, E ( Elisabetta ), Silvestrini, G ( Gabriella ), Fiocchi Malaspina, Elisabetta, Silvestrini, Gabriella, Fiocchi Malaspina, E ( Elisabetta ), and Silvestrini, G ( Gabriella )

Published
2023

13. A Cross-Indication Budget Impact Model of Secukinumab for the Treatment of Psoriasis, Psoriatic Arthritis, Ankylosing Spondylitis and Non-radiographic Axial Spondyloarthritis in Italy

Author

Cortesi, P, Fornari, C, Gisondi, P, Iannone, F, Antonazzo, I, Aloisi, E, Fiocchi, M, Ritrovato, D, Mantovani, L, Cortesi P. A., Fornari C., Gisondi P., Iannone F., Antonazzo I. C., Aloisi E., Fiocchi M., Ritrovato D., Mantovani L. G., Cortesi, P, Fornari, C, Gisondi, P, Iannone, F, Antonazzo, I, Aloisi, E, Fiocchi, M, Ritrovato, D, Mantovani, L, Cortesi P. A., Fornari C., Gisondi P., Iannone F., Antonazzo I. C., Aloisi E., Fiocchi M., Ritrovato D., and Mantovani L. G.

Abstract

Background: Recent developments improved outcomes in patients with autoimmune diseases. Biologics were approved as first-line treatment in selected naïve patients with plaque psoriasis (PsO), psoriatic arthritis (PsA), ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA). Among them, secukinumab was most recently approved for treatment of active nr-axSpA in adults. In this work, we assessed the budget impact of new secukinumab treatment options in the Italian market. Methods: A cross-indication budget impact model was designed to estimate the effects of adding secukinumab in the Italian market from the National Health System perspective over a 3-year period. The model included all adults with PsO, PsA, AS and nr-axSpA, treated with biologics or biosimilars. It compared costs between two scenarios, secukinumab availability or absence, for the four diseases combined and taken individually. A sensitivity analyses was conducted. Results: There were 68,121 adult patients treated with biologics in 2021 and 68,341 in 2023. The budget impact analysis (BIA) on all indications showed a cost reduction of €33.7 million (− 1.5%) over 3 years with the introduction of secukinumab. PsA patients had the highest saving (− €34.9 million), followed by PsO patients (− €7.8 million). Cost saving in PsO patients was balanced by increased budget reported in AS patients (+ €8.0 million). In nr-axSpA patients, secukinumab reported no significant budget increase (+ 1.0%). Conclusion: This BIA accounted for the new indication of secukinumab in nr-axSpA patients, reporting no significant changes in the required budget and adding an effective treatment option. Considering all indications, secukinumab is a sustainable treatment option.

Published
2023

14. Introduction

Author

Fiocchi Malaspina, Elisabetta, Silvestrini, Gabriella, Fiocchi Malaspina, E ( Elisabetta ), Silvestrini, G ( Gabriella ), Fiocchi Malaspina, Elisabetta, Silvestrini, Gabriella, Fiocchi Malaspina, E ( Elisabetta ), and Silvestrini, G ( Gabriella )

Published
2023

15. Natural Law and the Law of Nations in Eighteenth- and Nineteenth-Century Italy

Author

Fiocchi Malaspina, Elisabetta, Silvestrini, Gabriella, Fiocchi Malaspina, E ( Elisabetta ), Silvestrini, G ( Gabriella ), Fiocchi Malaspina, Elisabetta, Silvestrini, Gabriella, Fiocchi Malaspina, E ( Elisabetta ), and Silvestrini, G ( Gabriella )

Abstract

This volume sheds new light on modern theories of natural law through the lens of the fragmented political contexts of Italy in the eighteenth and nineteenth centuries, and the dramatic changes of the times. From the age of reforms, through revolution and the ‘Risorgimento’, the unification movement which ended with the creation of the unified Kingdom of Italy in 1861, we see a move from natural law and the law of nations to international law, whose teaching was introduced in Italian universities of the newly created Kingdom. The essays collected here show that natural law was not only the subject of a highly codified academic teaching, but also provided a broader conceptual and philosophical frame underlying the ‘science of man’. Natural law is also a language wherein reform programmes of education and of politics have taken form, affecting a variety of discourses and literary genres.

Published
2023

17. Editorial and Acknowledgements

Author

Romein, Christel Annemieke, Volkaert, Florenz, Wagner, Andreas, Malaspina, Elisabetta Fiocchi, Bellis-Phan, Nga, Dijck, Gijs van, Costa, Arthur Barretto de Almeida, Robertson, Stephen, Heirbaut, Dirk, Romein, Christel Annemieke, Volkaert, Florenz, Wagner, Andreas, Malaspina, Elisabetta Fiocchi, Bellis-Phan, Nga, Dijck, Gijs van, Costa, Arthur Barretto de Almeida, Robertson, Stephen, and Heirbaut, Dirk

Published
2023

20. Rhinitis associated with asthma is distinct from rhinitis alone:The ARIA-MeDALL hypothesis

Author

Bousquet, J, Melén, E, Haahtela, T, Koppelman, G H, Togias, A, Valenta, R, Akdis, C A, Czarlewski, W, Rothenberg, M, Valiulis, A, Wickman, M, Akdis, M, Aguilar, D, Bedbrook, A, Bindslev-Jensen, C, Bosnic-Anticevich, S, Boulet, L P, Brightling, C E, Brussino, L, Burte, E, Bustamante, M, Canonica, G W, Cecchi, L, Celedon, J C, Chaves Loureiro, C, Costa, E, Cruz, A A, Erhola, M, Gemicioglu, B, Fokkens, W J, Garcia-Aymerich, J, Guerra, S, Heinrich, J, Ivancevich, J C, Keil, T, Klimek, L, Kuna, P, Kupczyk, M, Kvedariene, V, Larenas-Linnemann, D E, Lemonnier, N, Lodrup Carlsen, K C, Louis, R, Makela, M, Makris, M, Maurer, M, Momas, I, Morais-Almeida, M, Mullol, J, Naclerio, R N, Nadeau, K, Nadif, R, Niedoszytko, M, Okamoto, Y, Ollert, M, Papadopoulos, N G, Passalacqua, G, Patella, V, Pawankar, R, Pham-Thi, N, Pfaar, O, Regateiro, F S, Ring, J, Rouadi, P W, Samolinski, B, Sastre, J, Savouré, M, Scichilone, N, Shamji, M H, Sheikh, A, Siroux, V, Sousa-Pinto, B, Standl, M, Sunyer, J, Taborda-Barata, L, Toppila-Salmi, S, Torres, M J, Tsiligianni, I, Valovirta, E, Vandenplas, O, Ventura, M T, Weiss, S, Yorgancioglu, A, Zhang, L, Abdul Latiff, A H, Aberer, W, Agache, I, Al-Ahmad, M, Alobid, I, Ansotegui, I J, Arshad, S H, Asayag, E, Barbara, C, Baharudin, A, Battur, L, Bennoor, K S, Berghea, E C, Bergmann, K C, Bernstein, D, Bewick, M, Blain, H, Bonini, M, Braido, F, Buhl, R, Bumbacea, R S, Bush, A, Calderon, M, Calvo-Gil, M, Camargos, P, Caraballo, L, Cardona, V, Carr, W, Carreiro-Martins, P, Casale, T, Cepeda Sarabia, A M, Chandrasekharan, R, Charpin, D, Chen, Y Z, Cherrez-Ojeda, I, Chivato, T, Chkhartishvili, E, Christoff, G, Chu, D K, Cingi, C, Correia de Sousa, J, Corrigan, C, Custovic, A, D'Amato, G, Del Giacco, S, De Blay, F, Devillier, P, Didier, A, do Ceu Teixeira, M, Dokic, D, Douagui, H, Doulaptsi, M, Durham, S, Dykewicz, M, Eiwegger, T, El-Sayed, Z A, Emuzyte, R, Fiocchi, A, Fyhrquist, N, Gomez, R M, Gotua, M, Guzman, M A, Hagemann, J, Hamamah, S, Halken, S, Halpin, D M G, Hofmann, M, Hossny, E, Hrubiško, M, Irani, C, Ispayeva, Z, Jares, E, Jartti, T, Jassem, E, Julge, K, Just, J, Jutel, M, Kaidashev, I, Kalayci, O, Kalyoncu, A F, Kardas, P, Kirenga, B, Kraxner, H, Kull, I, Kulus, M, La Grutta, S, Lau, S, Le Tuyet Thi, L, Levin, M, Lipworth, B, Lourenço, O, Mahboub, B, Martinez-Infante, E, Matricardi, P, Miculinic, N, Migueres, N, Mihaltan, F, Mohammad, Y, Moniuszko, M, Montefort, S, Neffen, H, Nekam, K, Nunes, E, Nyembue Tshipukane, D, O'Hehir, R, Ogulur, I, Ohta, K, Okubo, K, Ouedraogo, S, Olze, H, Pali-Schöll, I, Palomares, O, Palosuo, K, Panaitescu, C, Panzner, P, Park, H S, Pitsios, C, Plavec, D, Popov, T A, Puggioni, F, Quirce, S, Recto, M, Repka-Ramirez, M S, Robalo Cordeiro, C, Roche, N, Rodriguez-Gonzalez, M, Romantowski, J, Rosario Filho, N, Rottem, M, Sagara, H, Serpa, F S, Sayah, Z, Scheire, S, Schmid-Grendelmeier, P, Sisul, J C, Sole, D, Soto-Martinez, M, Sova, M, Sperl, A, Spranger, O, Stelmach, R, Suppli Ulrik, C, Thomas, M, To, T, Todo-Bom, A, Tomazic, P V, Urrutia-Pereira, M, Valentin-Rostan, M, Van Ganse, E, van Hage, M, Vasankari, T, Vichyanond, P, Viegi, G, Wallace, D, Wang, D Y, Williams, S, Worm, M, Yiallouros, P, Yusuf, O, Zaitoun, F, Zernotti, M, Zidarn, M, Zuberbier, J, Fonseca, J A, Zuberbier, T, Anto, J M, Bousquet, J, Melén, E, Haahtela, T, Koppelman, G H, Togias, A, Valenta, R, Akdis, C A, Czarlewski, W, Rothenberg, M, Valiulis, A, Wickman, M, Akdis, M, Aguilar, D, Bedbrook, A, Bindslev-Jensen, C, Bosnic-Anticevich, S, Boulet, L P, Brightling, C E, Brussino, L, Burte, E, Bustamante, M, Canonica, G W, Cecchi, L, Celedon, J C, Chaves Loureiro, C, Costa, E, Cruz, A A, Erhola, M, Gemicioglu, B, Fokkens, W J, Garcia-Aymerich, J, Guerra, S, Heinrich, J, Ivancevich, J C, Keil, T, Klimek, L, Kuna, P, Kupczyk, M, Kvedariene, V, Larenas-Linnemann, D E, Lemonnier, N, Lodrup Carlsen, K C, Louis, R, Makela, M, Makris, M, Maurer, M, Momas, I, Morais-Almeida, M, Mullol, J, Naclerio, R N, Nadeau, K, Nadif, R, Niedoszytko, M, Okamoto, Y, Ollert, M, Papadopoulos, N G, Passalacqua, G, Patella, V, Pawankar, R, Pham-Thi, N, Pfaar, O, Regateiro, F S, Ring, J, Rouadi, P W, Samolinski, B, Sastre, J, Savouré, M, Scichilone, N, Shamji, M H, Sheikh, A, Siroux, V, Sousa-Pinto, B, Standl, M, Sunyer, J, Taborda-Barata, L, Toppila-Salmi, S, Torres, M J, Tsiligianni, I, Valovirta, E, Vandenplas, O, Ventura, M T, Weiss, S, Yorgancioglu, A, Zhang, L, Abdul Latiff, A H, Aberer, W, Agache, I, Al-Ahmad, M, Alobid, I, Ansotegui, I J, Arshad, S H, Asayag, E, Barbara, C, Baharudin, A, Battur, L, Bennoor, K S, Berghea, E C, Bergmann, K C, Bernstein, D, Bewick, M, Blain, H, Bonini, M, Braido, F, Buhl, R, Bumbacea, R S, Bush, A, Calderon, M, Calvo-Gil, M, Camargos, P, Caraballo, L, Cardona, V, Carr, W, Carreiro-Martins, P, Casale, T, Cepeda Sarabia, A M, Chandrasekharan, R, Charpin, D, Chen, Y Z, Cherrez-Ojeda, I, Chivato, T, Chkhartishvili, E, Christoff, G, Chu, D K, Cingi, C, Correia de Sousa, J, Corrigan, C, Custovic, A, D'Amato, G, Del Giacco, S, De Blay, F, Devillier, P, Didier, A, do Ceu Teixeira, M, Dokic, D, Douagui, H, Doulaptsi, M, Durham, S, Dykewicz, M, Eiwegger, T, El-Sayed, Z A, Emuzyte, R, Fiocchi, A, Fyhrquist, N, Gomez, R M, Gotua, M, Guzman, M A, Hagemann, J, Hamamah, S, Halken, S, Halpin, D M G, Hofmann, M, Hossny, E, Hrubiško, M, Irani, C, Ispayeva, Z, Jares, E, Jartti, T, Jassem, E, Julge, K, Just, J, Jutel, M, Kaidashev, I, Kalayci, O, Kalyoncu, A F, Kardas, P, Kirenga, B, Kraxner, H, Kull, I, Kulus, M, La Grutta, S, Lau, S, Le Tuyet Thi, L, Levin, M, Lipworth, B, Lourenço, O, Mahboub, B, Martinez-Infante, E, Matricardi, P, Miculinic, N, Migueres, N, Mihaltan, F, Mohammad, Y, Moniuszko, M, Montefort, S, Neffen, H, Nekam, K, Nunes, E, Nyembue Tshipukane, D, O'Hehir, R, Ogulur, I, Ohta, K, Okubo, K, Ouedraogo, S, Olze, H, Pali-Schöll, I, Palomares, O, Palosuo, K, Panaitescu, C, Panzner, P, Park, H S, Pitsios, C, Plavec, D, Popov, T A, Puggioni, F, Quirce, S, Recto, M, Repka-Ramirez, M S, Robalo Cordeiro, C, Roche, N, Rodriguez-Gonzalez, M, Romantowski, J, Rosario Filho, N, Rottem, M, Sagara, H, Serpa, F S, Sayah, Z, Scheire, S, Schmid-Grendelmeier, P, Sisul, J C, Sole, D, Soto-Martinez, M, Sova, M, Sperl, A, Spranger, O, Stelmach, R, Suppli Ulrik, C, Thomas, M, To, T, Todo-Bom, A, Tomazic, P V, Urrutia-Pereira, M, Valentin-Rostan, M, Van Ganse, E, van Hage, M, Vasankari, T, Vichyanond, P, Viegi, G, Wallace, D, Wang, D Y, Williams, S, Worm, M, Yiallouros, P, Yusuf, O, Zaitoun, F, Zernotti, M, Zidarn, M, Zuberbier, J, Fonseca, J A, Zuberbier, T, and Anto, J M

Abstract

Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of “one-airway-one-disease,” coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the “Epithelial Barrier Hypothesis.” This review determined that the “one-airway-one-disease” concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme “allergic” (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono- or pauci-sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases., Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of "one-airway-one-disease," coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the "Epithelial Barrier Hypothesis." This review determined that the "one-airway-one-disease" concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme "allergic" (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono- or pauci-sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases.

Published
2023

21. Pre-ataxic loss of intrinsic plasticity and motor learning in a mouse model of SCA1

Author

Osório, Catarina, White, Joshua J., Lu, Heiling, Beekhof, Gerrit C., Fiocchi, Francesca Romana, Andriessen, Charlotte A., Dijkhuizen, Stephanie, Post, Laura, Schonewille, Martijn, Osório, Catarina, White, Joshua J., Lu, Heiling, Beekhof, Gerrit C., Fiocchi, Francesca Romana, Andriessen, Charlotte A., Dijkhuizen, Stephanie, Post, Laura, and Schonewille, Martijn

Abstract

Spinocerebellar ataxias are neurodegenerative diseases, the hallmark symptom of which is the development of ataxia due to cerebellar dysfunction. Purkinje cells, the principal neurons of the cerebellar cortex, are the main cells affected in these disorders, but the sequence of pathological events leading to their dysfunction is poorly understood. Understanding the origins of Purkinje cells dysfunction before it manifests is imperative to interpret the functional and behavioural consequences of cerebellar-related disorders, providing an optimal timeline for therapeutic interventions. Here, we report the cascade of events leading to Purkinje cells dysfunction before the onset of ataxia in a mouse model of spinocerebellar ataxia 1 (SCA1). Spatiotemporal characterization of the ATXN1[82Q] SCA1 mouse model revealed high levels of the mutant ATXN1[82Q] weeks before the onset of ataxia. The expression of the toxic protein first caused a reduction of Purkinje cells intrinsic excitability, which was followed by atrophy of Purkinje cells dendrite arborization and aberrant glutamatergic signalling, finally leading to disruption of Purkinje cells innervation of climbing fibres and loss of intrinsic plasticity of Purkinje cells. Functionally, we found that deficits in eyeblink conditioning, a form of cerebellum-dependent motor learning, precede the onset of ataxia, matching the timeline of climbing fibre degeneration and reduced intrinsic plasticity. Together, our results suggest that abnormal synaptic signalling and intrinsic plasticity during the pre-ataxia stage of spinocerebellar ataxias underlie an aberrant cerebellar circuitry that anticipates the full extent of the disease severity. Furthermore, our work indicates the potential for eyeblink conditioning to be used as a sensitive tool to detect early cerebellar dysfunction as a sign of future disease.

Published
2023

22. Rhinitis associated with asthma is distinct from rhinitis alone: The ARIA-MeDALL hypothesis

Author

Bousquet, J, Melén, E, Haahtela, T, Koppelman, G H, Togias, A, Valenta, R, Akdis, C A, Czarlewski, W, Rothenberg, M, Valiulis, A, Wickmann, M, Aguilar, D, Akdis, M, Ansotegui, I J, Barbara, C, Bedbrook, A, Bindslev Jensen, C, Bosnic-Anticevich, S, Boulet, L P, Brightling, C E, Brussino, L, Burte, E, Bustamante, M, Canonica, G W, Cecchi, L, Celedon, J C, Chaves-Loureiro, C, Costa, E, Cruz, A A, Erhola, M, Gemicioglu, B, Fokkens, W J, Garcia Aymerich, J, Guerra, S, Heinrich, J, Ivancevich, J C, Keil, T, Klimek, L, Kuna, P, Kupczyk, M, Kvedariene, V, Larenas-Linnemann, D E, Lemonnier, N, Lodrup Carlsen, K C, Louis, R, Makris, M, Maurer, M, Momas, I, Morais-Almeida, M, Mullol, J, Naclerio, R N, Nadeau, K, Nadif, R, Niedoszytko, M, Okamoto, Y, Ollert, M, Papadopoulos, N G, Passalacqua, G, Patella, V, Pawankar, R, Pham-Thi, N, Pfaar, O, Regateiro, F S, Ring, J, Rouadi, P W, Samolinski, B, Sastre, J, Savouré, M, Scichilone, N, Shamji, M H, Sheikh, A, Siroux, V, Sousa-Pinto, B, Standl, M, Sunyer, J, Taborda-Barata, L, Toppila-Salmi, S, Torres, M J, Tsiligianni, I, Valovirta, E, Vandenplas, O, Ventura, M T, Weiss, S, Yorgancioglu, A, Zhang, L, Abdul Latiff, A H, Aberer, W, Agache, I, Al-Ahmad, M, Alobid, I, Arshad, H S, Asayag, E, Baharudin, A, Battur, L, Bennoor, K S, Berghea, E C, Bergmann, K C, Bernstein, D, Bewick, Michael, Blain, H, Bonini, M, Braido, F, Buhl, R, Bumbacea, R, Bush, A, Calderon, M, Calvo, G, Camargos, P, Caraballo, L, Cardona, V, Carr, W, Carreiro-Martins, P, Casale, T, Cepeda Sarabia, A M, Chandrasekharan, R, Charpin, D, Chen, Y Z, Cherrez-Ojeda, I, Chivato, T, Chkhartishvili, E, Christoff, G, Chu, D K, Cingi, C, Correia da Sousa, J, Corrigan, C, Custovic, A, D'Amato, G, Del Giacco, S, De Blay, F, Devillier, P, Didier, A, do Ceu Teixeira, M, Dokic, D, Douagui, H, Doulaptsi, M, Durham, S, Dykewicz, M, Eiwegger, T, El-Sayed, Z A, Emuzyte, R, Fiocchi, A, Fyhrquist, N, Gomez, R M, Gotua, M, Guzman, M A, Hagemann, J, Hamamah, S, Halken, S, Halpin, D M G, Hofmann, M, Hossny, E, Hrubiško, M, Irani, C, Ispayeva, Z, Jares, E, Jartti, T, Jassem, E, Julge, K, Just, J, Jutel, M, Kaidashev, I, Kalayci, O, Kalyoncu, O, Kardas, P, Kirenga, B, Kraxner, H, Kull, I, Kulus, M, La Gruta, S, Lau, S, Le Tuyet Thi, L, Levin, M, Lipworth, B, Lourenço, O, Mahboub, B, Mäkelä, M J, Martinez-Infante, E, Matricardi, P, Miculinic, N, Migueres, N, Mihaltan, F, Mohamad, Y, Moniusko, M, Montefort, S, Neffen, H, Nekam, K, Nunes, E, Nyembue Tshipukane, D, O'Hehir, R E, Ogulur, I, Ohta, K, Okubo, K, Ouedraogo, S, Olze, H, Pali-Schöll, I, Palomares, O, Palosuo, K, Panaitescu, C, Panzner, P, Park, H S, Pitsios, C, Plavec, D, Popov, T A, Puggioni, F, Quirce, S, Recto, M, Repka-Ramirez, R, Roballo-Cordeiro, C, Roche, N, Rodriguez-Gonzales, M, Romantowski, J, Rosario Filho, N, Rottem, M, Sagara, H, Sarquis-Serpa, F, Sayah, Z, Scheire, S, Schmid-Grendelmeier, P, Sisul, J C, Sole, D, Soto-Martinez, M, Sova, M, Sperl, A, Spranger, O, Stelmach, R, Suppli Ulrik, C, Thomas, M, To, T, Todo-Bom, A, Tomazic, P V, Urrutia-Pereira, M, Valentin-Rostan, M, van Ganse, E, Van Hage, M, Vasankari, T, Vichyanond, P, Viegi, G, Wallace, D, Wang, D Y, Williams, S, Worm, M, Yiallouros, P, Yusuf, O, Zaitoun, F, Zernotti, M, Zidarn, M, Zuberbier, J, Fonseca, J A, Zuberbier, T, Anto, J M, Bousquet, J, Melén, E, Haahtela, T, Koppelman, G H, Togias, A, Valenta, R, Akdis, C A, Czarlewski, W, Rothenberg, M, Valiulis, A, Wickmann, M, Aguilar, D, Akdis, M, Ansotegui, I J, Barbara, C, Bedbrook, A, Bindslev Jensen, C, Bosnic-Anticevich, S, Boulet, L P, Brightling, C E, Brussino, L, Burte, E, Bustamante, M, Canonica, G W, Cecchi, L, Celedon, J C, Chaves-Loureiro, C, Costa, E, Cruz, A A, Erhola, M, Gemicioglu, B, Fokkens, W J, Garcia Aymerich, J, Guerra, S, Heinrich, J, Ivancevich, J C, Keil, T, Klimek, L, Kuna, P, Kupczyk, M, Kvedariene, V, Larenas-Linnemann, D E, Lemonnier, N, Lodrup Carlsen, K C, Louis, R, Makris, M, Maurer, M, Momas, I, Morais-Almeida, M, Mullol, J, Naclerio, R N, Nadeau, K, Nadif, R, Niedoszytko, M, Okamoto, Y, Ollert, M, Papadopoulos, N G, Passalacqua, G, Patella, V, Pawankar, R, Pham-Thi, N, Pfaar, O, Regateiro, F S, Ring, J, Rouadi, P W, Samolinski, B, Sastre, J, Savouré, M, Scichilone, N, Shamji, M H, Sheikh, A, Siroux, V, Sousa-Pinto, B, Standl, M, Sunyer, J, Taborda-Barata, L, Toppila-Salmi, S, Torres, M J, Tsiligianni, I, Valovirta, E, Vandenplas, O, Ventura, M T, Weiss, S, Yorgancioglu, A, Zhang, L, Abdul Latiff, A H, Aberer, W, Agache, I, Al-Ahmad, M, Alobid, I, Arshad, H S, Asayag, E, Baharudin, A, Battur, L, Bennoor, K S, Berghea, E C, Bergmann, K C, Bernstein, D, Bewick, Michael, Blain, H, Bonini, M, Braido, F, Buhl, R, Bumbacea, R, Bush, A, Calderon, M, Calvo, G, Camargos, P, Caraballo, L, Cardona, V, Carr, W, Carreiro-Martins, P, Casale, T, Cepeda Sarabia, A M, Chandrasekharan, R, Charpin, D, Chen, Y Z, Cherrez-Ojeda, I, Chivato, T, Chkhartishvili, E, Christoff, G, Chu, D K, Cingi, C, Correia da Sousa, J, Corrigan, C, Custovic, A, D'Amato, G, Del Giacco, S, De Blay, F, Devillier, P, Didier, A, do Ceu Teixeira, M, Dokic, D, Douagui, H, Doulaptsi, M, Durham, S, Dykewicz, M, Eiwegger, T, El-Sayed, Z A, Emuzyte, R, Fiocchi, A, Fyhrquist, N, Gomez, R M, Gotua, M, Guzman, M A, Hagemann, J, Hamamah, S, Halken, S, Halpin, D M G, Hofmann, M, Hossny, E, Hrubiško, M, Irani, C, Ispayeva, Z, Jares, E, Jartti, T, Jassem, E, Julge, K, Just, J, Jutel, M, Kaidashev, I, Kalayci, O, Kalyoncu, O, Kardas, P, Kirenga, B, Kraxner, H, Kull, I, Kulus, M, La Gruta, S, Lau, S, Le Tuyet Thi, L, Levin, M, Lipworth, B, Lourenço, O, Mahboub, B, Mäkelä, M J, Martinez-Infante, E, Matricardi, P, Miculinic, N, Migueres, N, Mihaltan, F, Mohamad, Y, Moniusko, M, Montefort, S, Neffen, H, Nekam, K, Nunes, E, Nyembue Tshipukane, D, O'Hehir, R E, Ogulur, I, Ohta, K, Okubo, K, Ouedraogo, S, Olze, H, Pali-Schöll, I, Palomares, O, Palosuo, K, Panaitescu, C, Panzner, P, Park, H S, Pitsios, C, Plavec, D, Popov, T A, Puggioni, F, Quirce, S, Recto, M, Repka-Ramirez, R, Roballo-Cordeiro, C, Roche, N, Rodriguez-Gonzales, M, Romantowski, J, Rosario Filho, N, Rottem, M, Sagara, H, Sarquis-Serpa, F, Sayah, Z, Scheire, S, Schmid-Grendelmeier, P, Sisul, J C, Sole, D, Soto-Martinez, M, Sova, M, Sperl, A, Spranger, O, Stelmach, R, Suppli Ulrik, C, Thomas, M, To, T, Todo-Bom, A, Tomazic, P V, Urrutia-Pereira, M, Valentin-Rostan, M, van Ganse, E, Van Hage, M, Vasankari, T, Vichyanond, P, Viegi, G, Wallace, D, Wang, D Y, Williams, S, Worm, M, Yiallouros, P, Yusuf, O, Zaitoun, F, Zernotti, M, Zidarn, M, Zuberbier, J, Fonseca, J A, Zuberbier, T, and Anto, J M

Abstract

Asthma, rhinitis and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of "one-airway-one-disease", coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitisation and multimorbidity, (iii) advances in mHealth for novel phenotype definition, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut and neuropsychiatric multimorbidities, is the "Epithelial Barrier Hypothesis". This review determined that the "one-airway-one-disease" concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme "allergic" (asthma) phenotype combining asthma, rhinitis and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitisation patterns (mono- or pauci-sensitisation versus polysensitisation), (iii) severity of symptoms and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and auto-immune diseases. [Abstract copyright: This article is protected by copyright. All rights reserved.]

Published
2023

24. The Athena X-ray Integral Field Unit: a consolidated design for the system requirement review of the preliminary definition phase

Author

Universidad de Alicante. Departamento de Física, Ingeniería de Sistemas y Teoría de la Señal, Universidad de Alicante. Instituto Universitario de Física Aplicada a las Ciencias y las Tecnologías, Barret, Didier, Albouys, Vincent, den Herder, Jan-Willem, Piro, Luigi, Cappi, Massimo, Huovelin, Juhani, Kelley, Richard, Mas-Hesse, J. Miguel, Paltani, Stéphane, Rauw, Gregor, Rozanska, Agata, Bernard, Vivian, Berrocal, Alicia, Audard, Marc, Blin, Sylvie, Bonino, Donata, Frericks, Martin, Bonnet, François, Bonny, Patrick, Boorman, Peter, Ptak, Andy, Chaoul, Laurence, Boreux, Charles, Bounab, Ayoub, Boutelier, Martin, Boyce, Kevin, Brienza, Daniele, Bandler, Simon, Bruijn, Marcel, Gabici, Stefano, Bulgarelli, Andrea, Calarco, Simona, Raulin, Desi, Gloaguen, Emilie, Callanan, Paul, Prada Campello, Alberto, Camus, Thierry, Canourgues, Florent, Capobianco, Vito, Cardiel, Nicolas, Castellani, Florent, Barbera, Marco, Gant, Florent, Simionescu, Aurora, Cheatom, Oscar, Doumayrou, Eric, Chervenak, James, Chiarello, Fabio, Clerc, Laurent, Clerc, Nicolas, Cobo, Beatriz, Coeur-Joly, Odile, Coleiro, Alexis, Colonges, Stéphane, Torrejon, Jose M., Corcione, Leonardo, Gao, Jian-Rong, Puccetti, Simonetta, Barcons, Xavier, Coriat, Mickael, Coynel, Alexandre, Cuttaia, Francesco, D’Ai, Antonino, D’anca, Fabio, Dadina, Mauro, Acero, Fabio, Daniel, Christophe, Dauner, Lea, DeNigris, Natalie, Puccio, Elena, Gastaldello, Fabio, Dercksen, Johannes, Bozzo, Enrico, DiPirro, Michael, Genolet, Ludovic, Durkin, Malcom, van Leeuwen, Bert-Joost, Charles, Ivan, Ghizzardi, Simona, Alcacera Gil, M. Angeles, Giovannini, Elisa, Ramon, Pascale, Godet, Olivier, Gomez-Elvira, Javier, Gonzalez, Raoul, Gonzalez, Manuel, Gottardi, Luciano, Branduardi-Raymont, Graziella, Granat, Dolorès, Fioretti, Valentina, Gros, Michel, Costantini, Elisa, Guignard, Nicolas, Reina, Manuel, Hieltjes, Paul, Hurtado, Adolfo Jesús, Irwin, Kent, Jacquey, Christian, Ettori, Stefano, Janiuk, Agnieszka, Jaubert, Jean, Jiménez, Maria, Geoffray, Hervé, Jolly, Antoine, Jourdan, Thierry, Rioland, Guillaume, Dauser, Thomas, Julien, Sabine, Kedziora, Bartosz, Finoguenov, Alexis, Korb, Andrew, Kreykenbohm, Ingo, König, Ole, Langer, Mathieu, Laudet, Philippe, Jacques, Lionel, Laurent, Philippe, Rodriguez, Louis, Laurenza, Monica, Lesrel, Jean, Etcheverry, Christophe, Decourchelle, Anne, Ligori, Sebastiano, Lorenz, Maximilian, Luminari, Alfredo, Maffei, Bruno, Maisonnave, Océane, Marelli, Lorenzo, Kirsch, Christian, Roig, Anton, Massonet, Didier, Petit, Pascal, Maussang, Irwin, Melchor, Alejandro Gonzalo, Le Mer, Isabelle, Duband, Lionel, San Millan, Francisco Javier, Millerioux, Jean-Pierre, Mineo, Teresa, Minervini, Gabriele, Molin, Alexeï, Gatti, Flavio, Grosso, Nicolas, Smith, Stephen, Monestes, David, Montinaro, Nicola, Mot, Baptiste, Murat, David, Nagayoshi, Kenichiro, Duval, Jean-Marc, Nazé, Yaël, Noguès, Loïc, Pailot, Damien, Kaastra, Jelle, Rollet, Bertrand, Panessa, Francesca, Adams, Joseph, Parodi, Luigi, Roncarelli, Mauro, Dubbeldam, Luc, Hoogeveen, Ruud, Roudil, Gilles, Rudnicki, Tomasz, Sanisidro, Julien, Mazzotta, Pasquale, Sciortino, Luisa, Silva, Vitor, Sordet, Michael, Soto-Aguilar, Javier, Spizzi, Pierre, Goldwurm, Andrea, Dupieux, Michel, Surace, Christian, Svoboda, Jiri, Fernández Sánchez, Miguel, Miller, Jon, Taralli, Emanuele, Terrasa, Guilhem, Terrier, Régis, Todaro, Michela, Ubertini, Pietro, Uslenghi, Michela, Vaate, Jan Geralt Bijd de, Dupourqué, Simon, Vaccaro, Davide, den Hartog, Roland, Miniutti, Giovanni, van der Hulst, Paul, Varisco, Salvatore, Varnière, Peggy, Vibert, Laurent, Vidriales, María, Villa, Fabrizio, Vodopivec, Boris Martin, Volpe, Angela, Durand, Jean Louis, Vries, Cor de, Nicastro, Fabrizio, Wakeham, Nicholas, Walmsley, Gavin, Kiviranta, Mikko, Jackson, Brian, Wise, Michael, Wit, Martin de, Woźniak, Grzegorz, Jonker, Peter, Kilbourne, Caroline, Eckert, Dominique, Sciortino, Salvatore, Korpela, Seppo, Macculi, Claudio, Mendez, Mariano, Mitsuda, Kazuhisa, van der Kuur, Jan, Molendi, Silvano, Pajot, François, Pointecouteau, Etienne, Porter, Frederick, Pratt, Gabriel W., van Loon, Dennis, Eiriz, Valvanera, Prêle, Damien, Ravera, Laurent, Sato, Kosuke, Schaye, Joop, Shinozaki, Keisuke, Ledot, Aurélien, Skup, Konrad, Soucek, Jan, Thibert, Tanguy, Yamaguchi, Hiroya, Vink, Jacco, Ercolani, Eric, Webb, Natalie, Beaumont, Sophie, Piconcelli, Enrico, Ceballos, Maria Teresa, Cucchetti, Edoardo, D’Andrea, Matteo, Eckart, Megan, Ferrando, Philippe, Kammoun, Elias, Lotti, Simone, Mesnager, Jean-Michel, Natalucci, Lorenzo, Lyautey, Bertrand, Pinto, Ciro, Peille, Philippe, Doriese, William, de Plaa, Jelle, Ardellier, Florence, Argan, Andrea, Bellouard, Elise, Carron, Jérôme, Cavazzuti, Elisabetta, Fiorini, Mauro, Khosropanah, Pourya, Encinas Plaza, Jose Miguel, Martin, Sylvain, Parot, Yann, Finkbeiner, Fred, Perry, James, Pinsard, Frederic, Pradines, Alice, Rigano, Manuela, Roelfsema, Peter, Schwander, Denis, Torrioli, Guido, Plaza, Borja, Ullom, Joel, Vera, Isabel, Medinaceli Villegas, Eduardo, Fiocchi, Mariateresa, Sakai, Kazuhiro, Zuchniak, Monika, Brachet, Frank, Lo Cicero, Ugo, van Weers, Henk, Wilms, Joern, Fiore, Fabrizio, Abdoelkariem, Shariefa, Adam, Thomas, Adami, Christophe, Aicardi, Corinne, Fossecave, Hervé, Akamatsu, Hiroki, Merino Alonso, Pablo Eleazar, Amato, Roberta, André, Jérôme, Angelinelli, Matteo, Poyatos, David, Anon-Cancela, Manuel, Yamasaki, Noriko, Anvar, Shebli, Atienza, Ricardo, Attard, Anthony, Franssen, Philippe, Auricchio, Natalia, Balado, Ana, Bancel, Florian, Barusso, Lorenzo Ferrari, Prouvé, Thomas, Bascuñan, Arturo, Universidad de Alicante. Departamento de Física, Ingeniería de Sistemas y Teoría de la Señal, Universidad de Alicante. Instituto Universitario de Física Aplicada a las Ciencias y las Tecnologías, Barret, Didier, Albouys, Vincent, den Herder, Jan-Willem, Piro, Luigi, Cappi, Massimo, Huovelin, Juhani, Kelley, Richard, Mas-Hesse, J. Miguel, Paltani, Stéphane, Rauw, Gregor, Rozanska, Agata, Bernard, Vivian, Berrocal, Alicia, Audard, Marc, Blin, Sylvie, Bonino, Donata, Frericks, Martin, Bonnet, François, Bonny, Patrick, Boorman, Peter, Ptak, Andy, Chaoul, Laurence, Boreux, Charles, Bounab, Ayoub, Boutelier, Martin, Boyce, Kevin, Brienza, Daniele, Bandler, Simon, Bruijn, Marcel, Gabici, Stefano, Bulgarelli, Andrea, Calarco, Simona, Raulin, Desi, Gloaguen, Emilie, Callanan, Paul, Prada Campello, Alberto, Camus, Thierry, Canourgues, Florent, Capobianco, Vito, Cardiel, Nicolas, Castellani, Florent, Barbera, Marco, Gant, Florent, Simionescu, Aurora, Cheatom, Oscar, Doumayrou, Eric, Chervenak, James, Chiarello, Fabio, Clerc, Laurent, Clerc, Nicolas, Cobo, Beatriz, Coeur-Joly, Odile, Coleiro, Alexis, Colonges, Stéphane, Torrejon, Jose M., Corcione, Leonardo, Gao, Jian-Rong, Puccetti, Simonetta, Barcons, Xavier, Coriat, Mickael, Coynel, Alexandre, Cuttaia, Francesco, D’Ai, Antonino, D’anca, Fabio, Dadina, Mauro, Acero, Fabio, Daniel, Christophe, Dauner, Lea, DeNigris, Natalie, Puccio, Elena, Gastaldello, Fabio, Dercksen, Johannes, Bozzo, Enrico, DiPirro, Michael, Genolet, Ludovic, Durkin, Malcom, van Leeuwen, Bert-Joost, Charles, Ivan, Ghizzardi, Simona, Alcacera Gil, M. Angeles, Giovannini, Elisa, Ramon, Pascale, Godet, Olivier, Gomez-Elvira, Javier, Gonzalez, Raoul, Gonzalez, Manuel, Gottardi, Luciano, Branduardi-Raymont, Graziella, Granat, Dolorès, Fioretti, Valentina, Gros, Michel, Costantini, Elisa, Guignard, Nicolas, Reina, Manuel, Hieltjes, Paul, Hurtado, Adolfo Jesús, Irwin, Kent, Jacquey, Christian, Ettori, Stefano, Janiuk, Agnieszka, Jaubert, Jean, Jiménez, Maria, Geoffray, Hervé, Jolly, Antoine, Jourdan, Thierry, Rioland, Guillaume, Dauser, Thomas, Julien, Sabine, Kedziora, Bartosz, Finoguenov, Alexis, Korb, Andrew, Kreykenbohm, Ingo, König, Ole, Langer, Mathieu, Laudet, Philippe, Jacques, Lionel, Laurent, Philippe, Rodriguez, Louis, Laurenza, Monica, Lesrel, Jean, Etcheverry, Christophe, Decourchelle, Anne, Ligori, Sebastiano, Lorenz, Maximilian, Luminari, Alfredo, Maffei, Bruno, Maisonnave, Océane, Marelli, Lorenzo, Kirsch, Christian, Roig, Anton, Massonet, Didier, Petit, Pascal, Maussang, Irwin, Melchor, Alejandro Gonzalo, Le Mer, Isabelle, Duband, Lionel, San Millan, Francisco Javier, Millerioux, Jean-Pierre, Mineo, Teresa, Minervini, Gabriele, Molin, Alexeï, Gatti, Flavio, Grosso, Nicolas, Smith, Stephen, Monestes, David, Montinaro, Nicola, Mot, Baptiste, Murat, David, Nagayoshi, Kenichiro, Duval, Jean-Marc, Nazé, Yaël, Noguès, Loïc, Pailot, Damien, Kaastra, Jelle, Rollet, Bertrand, Panessa, Francesca, Adams, Joseph, Parodi, Luigi, Roncarelli, Mauro, Dubbeldam, Luc, Hoogeveen, Ruud, Roudil, Gilles, Rudnicki, Tomasz, Sanisidro, Julien, Mazzotta, Pasquale, Sciortino, Luisa, Silva, Vitor, Sordet, Michael, Soto-Aguilar, Javier, Spizzi, Pierre, Goldwurm, Andrea, Dupieux, Michel, Surace, Christian, Svoboda, Jiri, Fernández Sánchez, Miguel, Miller, Jon, Taralli, Emanuele, Terrasa, Guilhem, Terrier, Régis, Todaro, Michela, Ubertini, Pietro, Uslenghi, Michela, Vaate, Jan Geralt Bijd de, Dupourqué, Simon, Vaccaro, Davide, den Hartog, Roland, Miniutti, Giovanni, van der Hulst, Paul, Varisco, Salvatore, Varnière, Peggy, Vibert, Laurent, Vidriales, María, Villa, Fabrizio, Vodopivec, Boris Martin, Volpe, Angela, Durand, Jean Louis, Vries, Cor de, Nicastro, Fabrizio, Wakeham, Nicholas, Walmsley, Gavin, Kiviranta, Mikko, Jackson, Brian, Wise, Michael, Wit, Martin de, Woźniak, Grzegorz, Jonker, Peter, Kilbourne, Caroline, Eckert, Dominique, Sciortino, Salvatore, Korpela, Seppo, Macculi, Claudio, Mendez, Mariano, Mitsuda, Kazuhisa, van der Kuur, Jan, Molendi, Silvano, Pajot, François, Pointecouteau, Etienne, Porter, Frederick, Pratt, Gabriel W., van Loon, Dennis, Eiriz, Valvanera, Prêle, Damien, Ravera, Laurent, Sato, Kosuke, Schaye, Joop, Shinozaki, Keisuke, Ledot, Aurélien, Skup, Konrad, Soucek, Jan, Thibert, Tanguy, Yamaguchi, Hiroya, Vink, Jacco, Ercolani, Eric, Webb, Natalie, Beaumont, Sophie, Piconcelli, Enrico, Ceballos, Maria Teresa, Cucchetti, Edoardo, D’Andrea, Matteo, Eckart, Megan, Ferrando, Philippe, Kammoun, Elias, Lotti, Simone, Mesnager, Jean-Michel, Natalucci, Lorenzo, Lyautey, Bertrand, Pinto, Ciro, Peille, Philippe, Doriese, William, de Plaa, Jelle, Ardellier, Florence, Argan, Andrea, Bellouard, Elise, Carron, Jérôme, Cavazzuti, Elisabetta, Fiorini, Mauro, Khosropanah, Pourya, Encinas Plaza, Jose Miguel, Martin, Sylvain, Parot, Yann, Finkbeiner, Fred, Perry, James, Pinsard, Frederic, Pradines, Alice, Rigano, Manuela, Roelfsema, Peter, Schwander, Denis, Torrioli, Guido, Plaza, Borja, Ullom, Joel, Vera, Isabel, Medinaceli Villegas, Eduardo, Fiocchi, Mariateresa, Sakai, Kazuhiro, Zuchniak, Monika, Brachet, Frank, Lo Cicero, Ugo, van Weers, Henk, Wilms, Joern, Fiore, Fabrizio, Abdoelkariem, Shariefa, Adam, Thomas, Adami, Christophe, Aicardi, Corinne, Fossecave, Hervé, Akamatsu, Hiroki, Merino Alonso, Pablo Eleazar, Amato, Roberta, André, Jérôme, Angelinelli, Matteo, Poyatos, David, Anon-Cancela, Manuel, Yamasaki, Noriko, Anvar, Shebli, Atienza, Ricardo, Attard, Anthony, Franssen, Philippe, Auricchio, Natalia, Balado, Ana, Bancel, Florian, Barusso, Lorenzo Ferrari, Prouvé, Thomas, and Bascuñan, Arturo

Abstract

The Athena X-ray Integral Unit (X-IFU) is the high resolution X-ray spectrometer studied since 2015 for flying in the mid-30s on the Athena space X-ray Observatory. Athena is a versatile observatory designed to address the Hot and Energetic Universe science theme, as selected in November 2013 by the Survey Science Committee. Based on a large format array of Transition Edge Sensors (TES), X-IFU aims to provide spatially resolved X-ray spectroscopy, with a spectral resolution of 2.5 eV (up to 7 keV) over a hexagonal field of view of 5 arc minutes (equivalent diameter). The X-IFU entered its System Requirement Review (SRR) in June 2022, at about the same time when ESA called for an overall X-IFU redesign (including the X-IFU cryostat and the cooling chain), due to an unanticipated cost overrun of Athena. In this paper, after illustrating the breakthrough capabilities of the X-IFU, we describe the instrument as presented at its SRR (i.e. in the course of its preliminary definition phase, so-called B1), browsing through all the subsystems and associated requirements. We then show the instrument budgets, with a particular emphasis on the anticipated budgets of some of its key performance parameters, such as the instrument efficiency, spectral resolution, energy scale knowledge, count rate capability, non X-ray background and target of opportunity efficiency. Finally, we briefly discuss the ongoing key technology demonstration activities, the calibration and the activities foreseen in the X-IFU Instrument Science Center, touch on communication and outreach activities, the consortium organisation and the life cycle assessment of X-IFU aiming at minimising the environmental footprint, associated with the development of the instrument. Thanks to the studies conducted so far on X-IFU, it is expected that along the design-to-cost exercise requested by ESA, the X-IFU will maintain flagship capabilities in spatially resolved high resolution X-ray spectroscopy, enabling most of th

Published
2023

25. Rhinitis associated with asthma is distinct from rhinitis alone: The ARIA-MeDALL hypothesis

Author

Bousquet, J, Melén, E, Haahtela, T, Koppelman, G H, Togias, A, Valenta, R, Akdis, C A, Czarlewski, W, Rothenberg, M, Valiulis, A, Wickmann, M, Aguilar, D, Akdis, M, Ansotegui, I J, Barbara, C, Bedbrook, A, Bindslev Jensen, C, Bosnic-Anticevich, S, Boulet, L P, Brightling, C E, Brussino, L, Burte, E, Bustamante, M, Canonica, G W, Cecchi, L, Celedon, J C, Chaves-Loureiro, C, Costa, E, Cruz, A A, Erhola, M, Gemicioglu, B, Fokkens, W J, Garcia Aymerich, J, Guerra, S, Heinrich, J, Ivancevich, J C, Keil, T, Klimek, L, Kuna, P, Kupczyk, M, Kvedariene, V, Larenas-Linnemann, D E, Lemonnier, N, Lodrup Carlsen, K C, Louis, R, Makris, M, Maurer, M, Momas, I, Morais-Almeida, M, Mullol, J, Naclerio, R N, Nadeau, K, Nadif, R, Niedoszytko, M, Okamoto, Y, Ollert, M, Papadopoulos, N G, Passalacqua, G, Patella, V, Pawankar, R, Pham-Thi, N, Pfaar, O, Regateiro, F S, Ring, J, Rouadi, P W, Samolinski, B, Sastre, J, Savouré, M, Scichilone, N, Shamji, M H, Sheikh, A, Siroux, V, Sousa-Pinto, B, Standl, M, Sunyer, J, Taborda-Barata, L, Toppila-Salmi, S, Torres, M J, Tsiligianni, I, Valovirta, E, Vandenplas, O, Ventura, M T, Weiss, S, Yorgancioglu, A, Zhang, L, Abdul Latiff, A H, Aberer, W, Agache, I, Al-Ahmad, M, Alobid, I, Arshad, H S, Asayag, E, Baharudin, A, Battur, L, Bennoor, K S, Berghea, E C, Bergmann, K C, Bernstein, D, Bewick, Michael, Blain, H, Bonini, M, Braido, F, Buhl, R, Bumbacea, R, Bush, A, Calderon, M, Calvo, G, Camargos, P, Caraballo, L, Cardona, V, Carr, W, Carreiro-Martins, P, Casale, T, Cepeda Sarabia, A M, Chandrasekharan, R, Charpin, D, Chen, Y Z, Cherrez-Ojeda, I, Chivato, T, Chkhartishvili, E, Christoff, G, Chu, D K, Cingi, C, Correia da Sousa, J, Corrigan, C, Custovic, A, D'Amato, G, Del Giacco, S, De Blay, F, Devillier, P, Didier, A, do Ceu Teixeira, M, Dokic, D, Douagui, H, Doulaptsi, M, Durham, S, Dykewicz, M, Eiwegger, T, El-Sayed, Z A, Emuzyte, R, Fiocchi, A, Fyhrquist, N, Gomez, R M, Gotua, M, Guzman, M A, Hagemann, J, Hamamah, S, Halken, S, Halpin, D M G, Hofmann, M, Hossny, E, Hrubiško, M, Irani, C, Ispayeva, Z, Jares, E, Jartti, T, Jassem, E, Julge, K, Just, J, Jutel, M, Kaidashev, I, Kalayci, O, Kalyoncu, O, Kardas, P, Kirenga, B, Kraxner, H, Kull, I, Kulus, M, La Gruta, S, Lau, S, Le Tuyet Thi, L, Levin, M, Lipworth, B, Lourenço, O, Mahboub, B, Mäkelä, M J, Martinez-Infante, E, Matricardi, P, Miculinic, N, Migueres, N, Mihaltan, F, Mohamad, Y, Moniusko, M, Montefort, S, Neffen, H, Nekam, K, Nunes, E, Nyembue Tshipukane, D, O'Hehir, R E, Ogulur, I, Ohta, K, Okubo, K, Ouedraogo, S, Olze, H, Pali-Schöll, I, Palomares, O, Palosuo, K, Panaitescu, C, Panzner, P, Park, H S, Pitsios, C, Plavec, D, Popov, T A, Puggioni, F, Quirce, S, Recto, M, Repka-Ramirez, R, Roballo-Cordeiro, C, Roche, N, Rodriguez-Gonzales, M, Romantowski, J, Rosario Filho, N, Rottem, M, Sagara, H, Sarquis-Serpa, F, Sayah, Z, Scheire, S, Schmid-Grendelmeier, P, Sisul, J C, Sole, D, Soto-Martinez, M, Sova, M, Sperl, A, Spranger, O, Stelmach, R, Suppli Ulrik, C, Thomas, M, To, T, Todo-Bom, A, Tomazic, P V, Urrutia-Pereira, M, Valentin-Rostan, M, van Ganse, E, Van Hage, M, Vasankari, T, Vichyanond, P, Viegi, G, Wallace, D, Wang, D Y, Williams, S, Worm, M, Yiallouros, P, Yusuf, O, Zaitoun, F, Zernotti, M, Zidarn, M, Zuberbier, J, Fonseca, J A, Zuberbier, T, Anto, J M, Bousquet, J, Melén, E, Haahtela, T, Koppelman, G H, Togias, A, Valenta, R, Akdis, C A, Czarlewski, W, Rothenberg, M, Valiulis, A, Wickmann, M, Aguilar, D, Akdis, M, Ansotegui, I J, Barbara, C, Bedbrook, A, Bindslev Jensen, C, Bosnic-Anticevich, S, Boulet, L P, Brightling, C E, Brussino, L, Burte, E, Bustamante, M, Canonica, G W, Cecchi, L, Celedon, J C, Chaves-Loureiro, C, Costa, E, Cruz, A A, Erhola, M, Gemicioglu, B, Fokkens, W J, Garcia Aymerich, J, Guerra, S, Heinrich, J, Ivancevich, J C, Keil, T, Klimek, L, Kuna, P, Kupczyk, M, Kvedariene, V, Larenas-Linnemann, D E, Lemonnier, N, Lodrup Carlsen, K C, Louis, R, Makris, M, Maurer, M, Momas, I, Morais-Almeida, M, Mullol, J, Naclerio, R N, Nadeau, K, Nadif, R, Niedoszytko, M, Okamoto, Y, Ollert, M, Papadopoulos, N G, Passalacqua, G, Patella, V, Pawankar, R, Pham-Thi, N, Pfaar, O, Regateiro, F S, Ring, J, Rouadi, P W, Samolinski, B, Sastre, J, Savouré, M, Scichilone, N, Shamji, M H, Sheikh, A, Siroux, V, Sousa-Pinto, B, Standl, M, Sunyer, J, Taborda-Barata, L, Toppila-Salmi, S, Torres, M J, Tsiligianni, I, Valovirta, E, Vandenplas, O, Ventura, M T, Weiss, S, Yorgancioglu, A, Zhang, L, Abdul Latiff, A H, Aberer, W, Agache, I, Al-Ahmad, M, Alobid, I, Arshad, H S, Asayag, E, Baharudin, A, Battur, L, Bennoor, K S, Berghea, E C, Bergmann, K C, Bernstein, D, Bewick, Michael, Blain, H, Bonini, M, Braido, F, Buhl, R, Bumbacea, R, Bush, A, Calderon, M, Calvo, G, Camargos, P, Caraballo, L, Cardona, V, Carr, W, Carreiro-Martins, P, Casale, T, Cepeda Sarabia, A M, Chandrasekharan, R, Charpin, D, Chen, Y Z, Cherrez-Ojeda, I, Chivato, T, Chkhartishvili, E, Christoff, G, Chu, D K, Cingi, C, Correia da Sousa, J, Corrigan, C, Custovic, A, D'Amato, G, Del Giacco, S, De Blay, F, Devillier, P, Didier, A, do Ceu Teixeira, M, Dokic, D, Douagui, H, Doulaptsi, M, Durham, S, Dykewicz, M, Eiwegger, T, El-Sayed, Z A, Emuzyte, R, Fiocchi, A, Fyhrquist, N, Gomez, R M, Gotua, M, Guzman, M A, Hagemann, J, Hamamah, S, Halken, S, Halpin, D M G, Hofmann, M, Hossny, E, Hrubiško, M, Irani, C, Ispayeva, Z, Jares, E, Jartti, T, Jassem, E, Julge, K, Just, J, Jutel, M, Kaidashev, I, Kalayci, O, Kalyoncu, O, Kardas, P, Kirenga, B, Kraxner, H, Kull, I, Kulus, M, La Gruta, S, Lau, S, Le Tuyet Thi, L, Levin, M, Lipworth, B, Lourenço, O, Mahboub, B, Mäkelä, M J, Martinez-Infante, E, Matricardi, P, Miculinic, N, Migueres, N, Mihaltan, F, Mohamad, Y, Moniusko, M, Montefort, S, Neffen, H, Nekam, K, Nunes, E, Nyembue Tshipukane, D, O'Hehir, R E, Ogulur, I, Ohta, K, Okubo, K, Ouedraogo, S, Olze, H, Pali-Schöll, I, Palomares, O, Palosuo, K, Panaitescu, C, Panzner, P, Park, H S, Pitsios, C, Plavec, D, Popov, T A, Puggioni, F, Quirce, S, Recto, M, Repka-Ramirez, R, Roballo-Cordeiro, C, Roche, N, Rodriguez-Gonzales, M, Romantowski, J, Rosario Filho, N, Rottem, M, Sagara, H, Sarquis-Serpa, F, Sayah, Z, Scheire, S, Schmid-Grendelmeier, P, Sisul, J C, Sole, D, Soto-Martinez, M, Sova, M, Sperl, A, Spranger, O, Stelmach, R, Suppli Ulrik, C, Thomas, M, To, T, Todo-Bom, A, Tomazic, P V, Urrutia-Pereira, M, Valentin-Rostan, M, van Ganse, E, Van Hage, M, Vasankari, T, Vichyanond, P, Viegi, G, Wallace, D, Wang, D Y, Williams, S, Worm, M, Yiallouros, P, Yusuf, O, Zaitoun, F, Zernotti, M, Zidarn, M, Zuberbier, J, Fonseca, J A, Zuberbier, T, and Anto, J M

Abstract

Asthma, rhinitis and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of "one-airway-one-disease", coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitisation and multimorbidity, (iii) advances in mHealth for novel phenotype definition, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut and neuropsychiatric multimorbidities, is the "Epithelial Barrier Hypothesis". This review determined that the "one-airway-one-disease" concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme "allergic" (asthma) phenotype combining asthma, rhinitis and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitisation patterns (mono- or pauci-sensitisation versus polysensitisation), (iii) severity of symptoms and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and auto-immune diseases. [Abstract copyright: This article is protected by copyright. All rights reserved.]

Published
2023

26. Rhinitis associated with asthma is distinct from rhinitis alone: The ARIA-MeDALL hypothesis

Author

Bousquet, J, Melén, E, Haahtela, T, Koppelman, G H, Togias, A, Valenta, R, Akdis, C A, Czarlewski, W, Rothenberg, M, Valiulis, A, Wickmann, M, Aguilar, D, Akdis, M, Ansotegui, I J, Barbara, C, Bedbrook, A, Bindslev Jensen, C, Bosnic-Anticevich, S, Boulet, L P, Brightling, C E, Brussino, L, Burte, E, Bustamante, M, Canonica, G W, Cecchi, L, Celedon, J C, Chaves-Loureiro, C, Costa, E, Cruz, A A, Erhola, M, Gemicioglu, B, Fokkens, W J, Garcia Aymerich, J, Guerra, S, Heinrich, J, Ivancevich, J C, Keil, T, Klimek, L, Kuna, P, Kupczyk, M, Kvedariene, V, Larenas-Linnemann, D E, Lemonnier, N, Lodrup Carlsen, K C, Louis, R, Makris, M, Maurer, M, Momas, I, Morais-Almeida, M, Mullol, J, Naclerio, R N, Nadeau, K, Nadif, R, Niedoszytko, M, Okamoto, Y, Ollert, M, Papadopoulos, N G, Passalacqua, G, Patella, V, Pawankar, R, Pham-Thi, N, Pfaar, O, Regateiro, F S, Ring, J, Rouadi, P W, Samolinski, B, Sastre, J, Savouré, M, Scichilone, N, Shamji, M H, Sheikh, A, Siroux, V, Sousa-Pinto, B, Standl, M, Sunyer, J, Taborda-Barata, L, Toppila-Salmi, S, Torres, M J, Tsiligianni, I, Valovirta, E, Vandenplas, O, Ventura, M T, Weiss, S, Yorgancioglu, A, Zhang, L, Abdul Latiff, A H, Aberer, W, Agache, I, Al-Ahmad, M, Alobid, I, Arshad, H S, Asayag, E, Baharudin, A, Battur, L, Bennoor, K S, Berghea, E C, Bergmann, K C, Bernstein, D, Bewick, Michael, Blain, H, Bonini, M, Braido, F, Buhl, R, Bumbacea, R, Bush, A, Calderon, M, Calvo, G, Camargos, P, Caraballo, L, Cardona, V, Carr, W, Carreiro-Martins, P, Casale, T, Cepeda Sarabia, A M, Chandrasekharan, R, Charpin, D, Chen, Y Z, Cherrez-Ojeda, I, Chivato, T, Chkhartishvili, E, Christoff, G, Chu, D K, Cingi, C, Correia da Sousa, J, Corrigan, C, Custovic, A, D'Amato, G, Del Giacco, S, De Blay, F, Devillier, P, Didier, A, do Ceu Teixeira, M, Dokic, D, Douagui, H, Doulaptsi, M, Durham, S, Dykewicz, M, Eiwegger, T, El-Sayed, Z A, Emuzyte, R, Fiocchi, A, Fyhrquist, N, Gomez, R M, Gotua, M, Guzman, M A, Hagemann, J, Hamamah, S, Halken, S, Halpin, D M G, Hofmann, M, Hossny, E, Hrubiško, M, Irani, C, Ispayeva, Z, Jares, E, Jartti, T, Jassem, E, Julge, K, Just, J, Jutel, M, Kaidashev, I, Kalayci, O, Kalyoncu, O, Kardas, P, Kirenga, B, Kraxner, H, Kull, I, Kulus, M, La Gruta, S, Lau, S, Le Tuyet Thi, L, Levin, M, Lipworth, B, Lourenço, O, Mahboub, B, Mäkelä, M J, Martinez-Infante, E, Matricardi, P, Miculinic, N, Migueres, N, Mihaltan, F, Mohamad, Y, Moniusko, M, Montefort, S, Neffen, H, Nekam, K, Nunes, E, Nyembue Tshipukane, D, O'Hehir, R E, Ogulur, I, Ohta, K, Okubo, K, Ouedraogo, S, Olze, H, Pali-Schöll, I, Palomares, O, Palosuo, K, Panaitescu, C, Panzner, P, Park, H S, Pitsios, C, Plavec, D, Popov, T A, Puggioni, F, Quirce, S, Recto, M, Repka-Ramirez, R, Roballo-Cordeiro, C, Roche, N, Rodriguez-Gonzales, M, Romantowski, J, Rosario Filho, N, Rottem, M, Sagara, H, Sarquis-Serpa, F, Sayah, Z, Scheire, S, Schmid-Grendelmeier, P, Sisul, J C, Sole, D, Soto-Martinez, M, Sova, M, Sperl, A, Spranger, O, Stelmach, R, Suppli Ulrik, C, Thomas, M, To, T, Todo-Bom, A, Tomazic, P V, Urrutia-Pereira, M, Valentin-Rostan, M, van Ganse, E, Van Hage, M, Vasankari, T, Vichyanond, P, Viegi, G, Wallace, D, Wang, D Y, Williams, S, Worm, M, Yiallouros, P, Yusuf, O, Zaitoun, F, Zernotti, M, Zidarn, M, Zuberbier, J, Fonseca, J A, Zuberbier, T, Anto, J M, Bousquet, J, Melén, E, Haahtela, T, Koppelman, G H, Togias, A, Valenta, R, Akdis, C A, Czarlewski, W, Rothenberg, M, Valiulis, A, Wickmann, M, Aguilar, D, Akdis, M, Ansotegui, I J, Barbara, C, Bedbrook, A, Bindslev Jensen, C, Bosnic-Anticevich, S, Boulet, L P, Brightling, C E, Brussino, L, Burte, E, Bustamante, M, Canonica, G W, Cecchi, L, Celedon, J C, Chaves-Loureiro, C, Costa, E, Cruz, A A, Erhola, M, Gemicioglu, B, Fokkens, W J, Garcia Aymerich, J, Guerra, S, Heinrich, J, Ivancevich, J C, Keil, T, Klimek, L, Kuna, P, Kupczyk, M, Kvedariene, V, Larenas-Linnemann, D E, Lemonnier, N, Lodrup Carlsen, K C, Louis, R, Makris, M, Maurer, M, Momas, I, Morais-Almeida, M, Mullol, J, Naclerio, R N, Nadeau, K, Nadif, R, Niedoszytko, M, Okamoto, Y, Ollert, M, Papadopoulos, N G, Passalacqua, G, Patella, V, Pawankar, R, Pham-Thi, N, Pfaar, O, Regateiro, F S, Ring, J, Rouadi, P W, Samolinski, B, Sastre, J, Savouré, M, Scichilone, N, Shamji, M H, Sheikh, A, Siroux, V, Sousa-Pinto, B, Standl, M, Sunyer, J, Taborda-Barata, L, Toppila-Salmi, S, Torres, M J, Tsiligianni, I, Valovirta, E, Vandenplas, O, Ventura, M T, Weiss, S, Yorgancioglu, A, Zhang, L, Abdul Latiff, A H, Aberer, W, Agache, I, Al-Ahmad, M, Alobid, I, Arshad, H S, Asayag, E, Baharudin, A, Battur, L, Bennoor, K S, Berghea, E C, Bergmann, K C, Bernstein, D, Bewick, Michael, Blain, H, Bonini, M, Braido, F, Buhl, R, Bumbacea, R, Bush, A, Calderon, M, Calvo, G, Camargos, P, Caraballo, L, Cardona, V, Carr, W, Carreiro-Martins, P, Casale, T, Cepeda Sarabia, A M, Chandrasekharan, R, Charpin, D, Chen, Y Z, Cherrez-Ojeda, I, Chivato, T, Chkhartishvili, E, Christoff, G, Chu, D K, Cingi, C, Correia da Sousa, J, Corrigan, C, Custovic, A, D'Amato, G, Del Giacco, S, De Blay, F, Devillier, P, Didier, A, do Ceu Teixeira, M, Dokic, D, Douagui, H, Doulaptsi, M, Durham, S, Dykewicz, M, Eiwegger, T, El-Sayed, Z A, Emuzyte, R, Fiocchi, A, Fyhrquist, N, Gomez, R M, Gotua, M, Guzman, M A, Hagemann, J, Hamamah, S, Halken, S, Halpin, D M G, Hofmann, M, Hossny, E, Hrubiško, M, Irani, C, Ispayeva, Z, Jares, E, Jartti, T, Jassem, E, Julge, K, Just, J, Jutel, M, Kaidashev, I, Kalayci, O, Kalyoncu, O, Kardas, P, Kirenga, B, Kraxner, H, Kull, I, Kulus, M, La Gruta, S, Lau, S, Le Tuyet Thi, L, Levin, M, Lipworth, B, Lourenço, O, Mahboub, B, Mäkelä, M J, Martinez-Infante, E, Matricardi, P, Miculinic, N, Migueres, N, Mihaltan, F, Mohamad, Y, Moniusko, M, Montefort, S, Neffen, H, Nekam, K, Nunes, E, Nyembue Tshipukane, D, O'Hehir, R E, Ogulur, I, Ohta, K, Okubo, K, Ouedraogo, S, Olze, H, Pali-Schöll, I, Palomares, O, Palosuo, K, Panaitescu, C, Panzner, P, Park, H S, Pitsios, C, Plavec, D, Popov, T A, Puggioni, F, Quirce, S, Recto, M, Repka-Ramirez, R, Roballo-Cordeiro, C, Roche, N, Rodriguez-Gonzales, M, Romantowski, J, Rosario Filho, N, Rottem, M, Sagara, H, Sarquis-Serpa, F, Sayah, Z, Scheire, S, Schmid-Grendelmeier, P, Sisul, J C, Sole, D, Soto-Martinez, M, Sova, M, Sperl, A, Spranger, O, Stelmach, R, Suppli Ulrik, C, Thomas, M, To, T, Todo-Bom, A, Tomazic, P V, Urrutia-Pereira, M, Valentin-Rostan, M, van Ganse, E, Van Hage, M, Vasankari, T, Vichyanond, P, Viegi, G, Wallace, D, Wang, D Y, Williams, S, Worm, M, Yiallouros, P, Yusuf, O, Zaitoun, F, Zernotti, M, Zidarn, M, Zuberbier, J, Fonseca, J A, Zuberbier, T, and Anto, J M

Abstract

Asthma, rhinitis and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of "one-airway-one-disease", coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitisation and multimorbidity, (iii) advances in mHealth for novel phenotype definition, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut and neuropsychiatric multimorbidities, is the "Epithelial Barrier Hypothesis". This review determined that the "one-airway-one-disease" concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme "allergic" (asthma) phenotype combining asthma, rhinitis and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitisation patterns (mono- or pauci-sensitisation versus polysensitisation), (iii) severity of symptoms and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and auto-immune diseases. [Abstract copyright: This article is protected by copyright. All rights reserved.]

Published
2023

28. Rhinitis associated with asthma is distinct from rhinitis alone:The ARIA-MeDALL hypothesis

Author

Bousquet, J, Melén, E, Haahtela, T, Koppelman, G H, Togias, A, Valenta, R, Akdis, C A, Czarlewski, W, Rothenberg, M, Valiulis, A, Wickman, M, Akdis, M, Aguilar, D, Bedbrook, A, Bindslev-Jensen, C, Bosnic-Anticevich, S, Boulet, L P, Brightling, C E, Brussino, L, Burte, E, Bustamante, M, Canonica, G W, Cecchi, L, Celedon, J C, Chaves Loureiro, C, Costa, E, Cruz, A A, Erhola, M, Gemicioglu, B, Fokkens, W J, Garcia-Aymerich, J, Guerra, S, Heinrich, J, Ivancevich, J C, Keil, T, Klimek, L, Kuna, P, Kupczyk, M, Kvedariene, V, Larenas-Linnemann, D E, Lemonnier, N, Lodrup Carlsen, K C, Louis, R, Makela, M, Makris, M, Maurer, M, Momas, I, Morais-Almeida, M, Mullol, J, Naclerio, R N, Nadeau, K, Nadif, R, Niedoszytko, M, Okamoto, Y, Ollert, M, Papadopoulos, N G, Passalacqua, G, Patella, V, Pawankar, R, Pham-Thi, N, Pfaar, O, Regateiro, F S, Ring, J, Rouadi, P W, Samolinski, B, Sastre, J, Savouré, M, Scichilone, N, Shamji, M H, Sheikh, A, Siroux, V, Sousa-Pinto, B, Standl, M, Sunyer, J, Taborda-Barata, L, Toppila-Salmi, S, Torres, M J, Tsiligianni, I, Valovirta, E, Vandenplas, O, Ventura, M T, Weiss, S, Yorgancioglu, A, Zhang, L, Abdul Latiff, A H, Aberer, W, Agache, I, Al-Ahmad, M, Alobid, I, Ansotegui, I J, Arshad, S H, Asayag, E, Barbara, C, Baharudin, A, Battur, L, Bennoor, K S, Berghea, E C, Bergmann, K C, Bernstein, D, Bewick, M, Blain, H, Bonini, M, Braido, F, Buhl, R, Bumbacea, R S, Bush, A, Calderon, M, Calvo-Gil, M, Camargos, P, Caraballo, L, Cardona, V, Carr, W, Carreiro-Martins, P, Casale, T, Cepeda Sarabia, A M, Chandrasekharan, R, Charpin, D, Chen, Y Z, Cherrez-Ojeda, I, Chivato, T, Chkhartishvili, E, Christoff, G, Chu, D K, Cingi, C, Correia de Sousa, J, Corrigan, C, Custovic, A, D'Amato, G, Del Giacco, S, De Blay, F, Devillier, P, Didier, A, do Ceu Teixeira, M, Dokic, D, Douagui, H, Doulaptsi, M, Durham, S, Dykewicz, M, Eiwegger, T, El-Sayed, Z A, Emuzyte, R, Fiocchi, A, Fyhrquist, N, Gomez, R M, Gotua, M, Guzman, M A, Hagemann, J, Hamamah, S, Halken, S, Halpin, D M G, Hofmann, M, Hossny, E, Hrubiško, M, Irani, C, Ispayeva, Z, Jares, E, Jartti, T, Jassem, E, Julge, K, Just, J, Jutel, M, Kaidashev, I, Kalayci, O, Kalyoncu, A F, Kardas, P, Kirenga, B, Kraxner, H, Kull, I, Kulus, M, La Grutta, S, Lau, S, Le Tuyet Thi, L, Levin, M, Lipworth, B, Lourenço, O, Mahboub, B, Martinez-Infante, E, Matricardi, P, Miculinic, N, Migueres, N, Mihaltan, F, Mohammad, Y, Moniuszko, M, Montefort, S, Neffen, H, Nekam, K, Nunes, E, Nyembue Tshipukane, D, O'Hehir, R, Ogulur, I, Ohta, K, Okubo, K, Ouedraogo, S, Olze, H, Pali-Schöll, I, Palomares, O, Palosuo, K, Panaitescu, C, Panzner, P, Park, H S, Pitsios, C, Plavec, D, Popov, T A, Puggioni, F, Quirce, S, Recto, M, Repka-Ramirez, M S, Robalo Cordeiro, C, Roche, N, Rodriguez-Gonzalez, M, Romantowski, J, Rosario Filho, N, Rottem, M, Sagara, H, Serpa, F S, Sayah, Z, Scheire, S, Schmid-Grendelmeier, P, Sisul, J C, Sole, D, Soto-Martinez, M, Sova, M, Sperl, A, Spranger, O, Stelmach, R, Suppli Ulrik, C, Thomas, M, To, T, Todo-Bom, A, Tomazic, P V, Urrutia-Pereira, M, Valentin-Rostan, M, Van Ganse, E, van Hage, M, Vasankari, T, Vichyanond, P, Viegi, G, Wallace, D, Wang, D Y, Williams, S, Worm, M, Yiallouros, P, Yusuf, O, Zaitoun, F, Zernotti, M, Zidarn, M, Zuberbier, J, Fonseca, J A, Zuberbier, T, Anto, J M, Bousquet, J, Melén, E, Haahtela, T, Koppelman, G H, Togias, A, Valenta, R, Akdis, C A, Czarlewski, W, Rothenberg, M, Valiulis, A, Wickman, M, Akdis, M, Aguilar, D, Bedbrook, A, Bindslev-Jensen, C, Bosnic-Anticevich, S, Boulet, L P, Brightling, C E, Brussino, L, Burte, E, Bustamante, M, Canonica, G W, Cecchi, L, Celedon, J C, Chaves Loureiro, C, Costa, E, Cruz, A A, Erhola, M, Gemicioglu, B, Fokkens, W J, Garcia-Aymerich, J, Guerra, S, Heinrich, J, Ivancevich, J C, Keil, T, Klimek, L, Kuna, P, Kupczyk, M, Kvedariene, V, Larenas-Linnemann, D E, Lemonnier, N, Lodrup Carlsen, K C, Louis, R, Makela, M, Makris, M, Maurer, M, Momas, I, Morais-Almeida, M, Mullol, J, Naclerio, R N, Nadeau, K, Nadif, R, Niedoszytko, M, Okamoto, Y, Ollert, M, Papadopoulos, N G, Passalacqua, G, Patella, V, Pawankar, R, Pham-Thi, N, Pfaar, O, Regateiro, F S, Ring, J, Rouadi, P W, Samolinski, B, Sastre, J, Savouré, M, Scichilone, N, Shamji, M H, Sheikh, A, Siroux, V, Sousa-Pinto, B, Standl, M, Sunyer, J, Taborda-Barata, L, Toppila-Salmi, S, Torres, M J, Tsiligianni, I, Valovirta, E, Vandenplas, O, Ventura, M T, Weiss, S, Yorgancioglu, A, Zhang, L, Abdul Latiff, A H, Aberer, W, Agache, I, Al-Ahmad, M, Alobid, I, Ansotegui, I J, Arshad, S H, Asayag, E, Barbara, C, Baharudin, A, Battur, L, Bennoor, K S, Berghea, E C, Bergmann, K C, Bernstein, D, Bewick, M, Blain, H, Bonini, M, Braido, F, Buhl, R, Bumbacea, R S, Bush, A, Calderon, M, Calvo-Gil, M, Camargos, P, Caraballo, L, Cardona, V, Carr, W, Carreiro-Martins, P, Casale, T, Cepeda Sarabia, A M, Chandrasekharan, R, Charpin, D, Chen, Y Z, Cherrez-Ojeda, I, Chivato, T, Chkhartishvili, E, Christoff, G, Chu, D K, Cingi, C, Correia de Sousa, J, Corrigan, C, Custovic, A, D'Amato, G, Del Giacco, S, De Blay, F, Devillier, P, Didier, A, do Ceu Teixeira, M, Dokic, D, Douagui, H, Doulaptsi, M, Durham, S, Dykewicz, M, Eiwegger, T, El-Sayed, Z A, Emuzyte, R, Fiocchi, A, Fyhrquist, N, Gomez, R M, Gotua, M, Guzman, M A, Hagemann, J, Hamamah, S, Halken, S, Halpin, D M G, Hofmann, M, Hossny, E, Hrubiško, M, Irani, C, Ispayeva, Z, Jares, E, Jartti, T, Jassem, E, Julge, K, Just, J, Jutel, M, Kaidashev, I, Kalayci, O, Kalyoncu, A F, Kardas, P, Kirenga, B, Kraxner, H, Kull, I, Kulus, M, La Grutta, S, Lau, S, Le Tuyet Thi, L, Levin, M, Lipworth, B, Lourenço, O, Mahboub, B, Martinez-Infante, E, Matricardi, P, Miculinic, N, Migueres, N, Mihaltan, F, Mohammad, Y, Moniuszko, M, Montefort, S, Neffen, H, Nekam, K, Nunes, E, Nyembue Tshipukane, D, O'Hehir, R, Ogulur, I, Ohta, K, Okubo, K, Ouedraogo, S, Olze, H, Pali-Schöll, I, Palomares, O, Palosuo, K, Panaitescu, C, Panzner, P, Park, H S, Pitsios, C, Plavec, D, Popov, T A, Puggioni, F, Quirce, S, Recto, M, Repka-Ramirez, M S, Robalo Cordeiro, C, Roche, N, Rodriguez-Gonzalez, M, Romantowski, J, Rosario Filho, N, Rottem, M, Sagara, H, Serpa, F S, Sayah, Z, Scheire, S, Schmid-Grendelmeier, P, Sisul, J C, Sole, D, Soto-Martinez, M, Sova, M, Sperl, A, Spranger, O, Stelmach, R, Suppli Ulrik, C, Thomas, M, To, T, Todo-Bom, A, Tomazic, P V, Urrutia-Pereira, M, Valentin-Rostan, M, Van Ganse, E, van Hage, M, Vasankari, T, Vichyanond, P, Viegi, G, Wallace, D, Wang, D Y, Williams, S, Worm, M, Yiallouros, P, Yusuf, O, Zaitoun, F, Zernotti, M, Zidarn, M, Zuberbier, J, Fonseca, J A, Zuberbier, T, and Anto, J M

Abstract

Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of “one-airway-one-disease,” coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the “Epithelial Barrier Hypothesis.” This review determined that the “one-airway-one-disease” concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme “allergic” (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono- or pauci-sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases., Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of "one-airway-one-disease," coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the "Epithelial Barrier Hypothesis." This review determined that the "one-airway-one-disease" concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme "allergic" (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono- or pauci-sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases.

Published
2023

29. Interweaving Legal Sources for a Natural Law and Law of Nations across the Ocean: Domingo Muriel (1718-1795)

Author

Fiocchi Malaspina, Elisabetta, Di Chiara, Francesco, Demarchi, Giacomo, Rodriguez Arrocha, Belinda, Fiocchi Malaspina, E ( Elisabetta ), Di Chiara, F ( Francesco ), Demarchi, G ( Giacomo ), Rodriguez Arrocha, B ( Belinda ), Fiocchi Malaspina, Elisabetta, Di Chiara, Francesco, Demarchi, Giacomo, Rodriguez Arrocha, Belinda, Fiocchi Malaspina, E ( Elisabetta ), Di Chiara, F ( Francesco ), Demarchi, G ( Giacomo ), and Rodriguez Arrocha, B ( Belinda )

Published
2021

30. Micronutritional supplementation with a holoBLG-based FSMP (food for special medical purposes)-lozenge alleviates allergic symptoms in BALB/c mice: Imitating the protective farm effect

Author

Biomedical International R+D GmbH, Austrian Science Fund, Bencard Allergie GmbH, Afify, Sheriene Moussa [0000-0003-2082-9038], Pacios, Luis F [0000-0002-0585-4289], Redegeld, Frank A. [0000-0001-8830-7960], Pali-Schöll, Isabella [0000-0003-2089-6011], Hufnagl, Karin [0000-0002-2288-2468], Bianchini, Rodolfo [0000-0003-0351-6937], Guethoff, Sonja [0000-0001-5846-1035], Kramer, Matthias F [0000-0002-3740-4733], Fiocchi, Alessandro [0000-0002-2549-0523], Dvorak, Zdenek [0000-0002-3938-3585], Jensen-Jarolim, Erika [0000-0003-4019-5765], Roth-Walter, Franziska [0000-0001-5005-9228], Afify, Sheriene Moussa, Regner, Andreas, Pacios, Luis F., Blokhuis, Bart R., Jensen, Sebastian A, Redegeld, Frank A., Pali-Schöll, Isabella, Hufnagl, Karin, Bianchini, Rodolfo, Guethoff, Sonja, Kramer, Matthias F, Fiocchi, Alessandro, Dvorak, Zdenek, Jensen-Jarolim, Erika, Roth-Walter, Franziska, Biomedical International R+D GmbH, Austrian Science Fund, Bencard Allergie GmbH, Afify, Sheriene Moussa [0000-0003-2082-9038], Pacios, Luis F [0000-0002-0585-4289], Redegeld, Frank A. [0000-0001-8830-7960], Pali-Schöll, Isabella [0000-0003-2089-6011], Hufnagl, Karin [0000-0002-2288-2468], Bianchini, Rodolfo [0000-0003-0351-6937], Guethoff, Sonja [0000-0001-5846-1035], Kramer, Matthias F [0000-0002-3740-4733], Fiocchi, Alessandro [0000-0002-2549-0523], Dvorak, Zdenek [0000-0002-3938-3585], Jensen-Jarolim, Erika [0000-0003-4019-5765], Roth-Walter, Franziska [0000-0001-5005-9228], Afify, Sheriene Moussa, Regner, Andreas, Pacios, Luis F., Blokhuis, Bart R., Jensen, Sebastian A, Redegeld, Frank A., Pali-Schöll, Isabella, Hufnagl, Karin, Bianchini, Rodolfo, Guethoff, Sonja, Kramer, Matthias F, Fiocchi, Alessandro, Dvorak, Zdenek, Jensen-Jarolim, Erika, and Roth-Walter, Franziska

Abstract

Previously, the protective farm effect was imitated using the whey protein beta-lactoglobulin (BLG) that is spiked with iron-flavonoid complexes. Here, we formulated for clinical translation a lozenge as food for special medical purposes (FSMP) using catechin-iron complexes as ligands for BLG. The lozenge was tested in vitro and in a therapeutical BALB/c mice model.

Published
2021

31. Interweaving Legal Sources for a Natural Law and Law of Nations across the Ocean: Domingo Muriel (1718-1795)

Author

Fiocchi Malaspina, Elisabetta, Di Chiara, Francesco, Demarchi, Giacomo, Rodriguez Arrocha, Belinda, Fiocchi Malaspina, E ( Elisabetta ), Di Chiara, F ( Francesco ), Demarchi, G ( Giacomo ), Rodriguez Arrocha, B ( Belinda ), Fiocchi Malaspina, Elisabetta, Di Chiara, Francesco, Demarchi, Giacomo, Rodriguez Arrocha, Belinda, Fiocchi Malaspina, E ( Elisabetta ), Di Chiara, F ( Francesco ), Demarchi, G ( Giacomo ), and Rodriguez Arrocha, B ( Belinda )

Published
2021

32. Micronutritional supplementation with a holoBLG-based FSMP (food for special medical purposes)-lozenge alleviates allergic symptoms in BALB/c mice: Imitating the protective farm effect

Author

Afify, Sheriene Moussa, Regner, Andreas, Pacios, Luis F, Blokhuis, Bart R, Jensen, Sebastian A, Redegeld, Frank A, Pali-Schöll, Isabella, Hufnagl, Karin, Bianchini, Rodolfo, Guethoff, Sonja, Kramer, Matthias F, Fiocchi, Alessandro, Dvorak, Zdenek, Jensen-Jarolim, Erika, Roth-Walter, Franziska, Afify, Sheriene Moussa, Regner, Andreas, Pacios, Luis F, Blokhuis, Bart R, Jensen, Sebastian A, Redegeld, Frank A, Pali-Schöll, Isabella, Hufnagl, Karin, Bianchini, Rodolfo, Guethoff, Sonja, Kramer, Matthias F, Fiocchi, Alessandro, Dvorak, Zdenek, Jensen-Jarolim, Erika, and Roth-Walter, Franziska

Abstract

Background: Previously, the protective farm effect was imitated using the whey protein beta-lactoglobulin (BLG) that is spiked with iron-flavonoid complexes. Here, we formulated for clinical translation a lozenge as food for special medical purposes (FSMP) using catechin-iron complexes as ligands for BLG. The lozenge was tested in vitro and in a therapeutical BALB/c mice model. Methods: Binding of iron-catechin into BLG was confirmed by spectroscopy and docking calculations. Serum IgE binding of children allergic or tolerating milk was assessed to loaded (holo-) versus empty (apo-) BLG and for human mast cell degranulation. BLG and Bet v 1 double-sensitized mice were orally treated with the holoBLG or placebo lozenge, and immunologically analysed after systemic allergen challenge. Human PBMCs of pollen allergic subjects were flow cytometrically assessed after stimulation with apoBLG or holoBLG using catechin-iron complexes as ligands. Results: One major IgE and T cell epitope were masked by catechin-iron complexes, which impaired IgE binding of milk-allergic children and degranulation of mast cells. In mice, only supplementation with the holoBLG lozenge reduced clinical reactivity to BLG and Bet v 1, promoted Tregs, and suppressed antigen presentation. In allergic subjects, stimulation of PBMCs with holoBLG led to a significant increase of intracellular iron in circulating CD14+ cells with significantly lower expression of HLADR and CD86 compared to their stimulation with apoBLG. Conclusion: The FSMP lozenge targeted antigen presenting cells and dampened immune activation in human immune cells and allergic mice in an antigen-non-specific manner, thereby conferring immune resilience against allergic symptoms.

Published
2022

33. Improving Nursing Program Eligibility

Author

Dimian, Adel, Fiocchi, Luke, Gumuchian, Adrien, Hall, Cassie, Schweyen, Courtney, Rooney, Connor, Vanderwater, Matthew, Dimian, Adel, Fiocchi, Luke, Gumuchian, Adrien, Hall, Cassie, Schweyen, Courtney, Rooney, Connor, and Vanderwater, Matthew

Abstract

The demand for trained nurses is currently at an all-time high, and Carroll College is on the front lines of filling the demand for tomorrow’s nurses. Issues arise in the advancement process from pre-nursing into the official nursing program; where delays or roadblocks can lead to unfilled seats. A significant number of pre-nursing students are not eligible to enter the nursing program on schedule, often preventing them from graduating within four years. This can result in students changing majors or, worse, leaving Carroll College altogether. We used the D-M-A-I-C Six Sigma methodology to identify the key variables which lead to these negative outcomes and to answer whether the first-year course structure is impeding the advancement into the nursing program.

Published
2022

34. IGR J18249-3243: a new GeV-emitting FR II and the emerging population of high energy radio galaxies

Author

Bruni, G., Bassani, L., Persic, M., Rephaeli, Y., Malizia, A., Molina, M., Fiocchi, M., Ricci, R., Wieringa, M. H., Giroletti, M., Panessa, F., Bazzano, A., Ubertini, P., Bruni, G., Bassani, L., Persic, M., Rephaeli, Y., Malizia, A., Molina, M., Fiocchi, M., Ricci, R., Wieringa, M. H., Giroletti, M., Panessa, F., Bazzano, A., and Ubertini, P.

Abstract

The advent of new all-sky radio surveys such as the VLA Sky Survey (VLASS) and the Rapid ASKAP Continuum Survey (RACS), performed with the latest generation radio telescopes, is opening new possibilities on the classification and study of extragalactic $\gamma$-ray sources, specially the underrepresented ones like radio galaxies. In particular, the enhanced sensitivity (sub-mJy level) and resolution (a few arcsec) provides a better morphological and spectral classification. In this work, we present the reclassification of a Fermi-LAT source as a new FRII radio galaxy from the INTEGRAL sample found to emit at GeV energies. Through a broad-band spectral fitting from radio to $\gamma$-ray, we find that the commonly invoked jet contribution is not sufficient to account for the observed $\gamma$-ray flux. Our modeling suggests that the observed emission could mainly originate in the lobes (rather than in the radio core) by inverse Compton scattering of radio-emitting electrons off the ambient photon fields. In addition, we cross-correlated the latest generation radio surveys with a list of Fermi-LAT objects from the literature considered to be candidate misaligned AGN, finding four new radio galaxies with a double-lobed morphology. Additional four objects could be classified as such thanks to previous studies in the literature, for a total of nine new radio galaxies with GeV emission presented in this work. We foresee that further objects of this class might be found in the near future with the advent of the Square Kilometer Array (SKA), populating the GeV sky., Comment: Submitted to MNRAS

Published
2022
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35. Stimulus generalization in mice during Pavlovian eyeblink conditioning

Author

Fiocchi, F R, Dijkhuizen, S, Koekkoek, S K E, De Zeeuw, C I, Boele, H J, Fiocchi, F R, Dijkhuizen, S, Koekkoek, S K E, De Zeeuw, C I, and Boele, H J

Abstract

Here we investigate stimulus generalization in a cerebellar learning paradigm, called eyeblink conditioning. Mice were conditioned to close their eyes in response to a 10 kHz tone by repeatedly pairing this tone with an air puff to the eye 250 ms after tone onset. After ten consecutive days of training, when mice showed reliable conditioned eyelid responses to the 10 kHz tone, we started to expose them to tones with other frequencies, ranging from 2 to 20 kHz. We found that mice had a strong generalization gradient, whereby the probability and amplitude of conditioned eyelid responses gradually decreases depending on the dissimilarity with the 10 kHz tone. Tones with frequencies closest to 10kHz evoked the most and largest conditioned eyelid responses and each step away from the 10 kHz tone resulted in fewer and smaller conditioned responses. In addition, we found that tones with lower frequencies resulted in conditioned responses that peaked earlier after tone onset compared to those to tones with higher frequencies. Together, our data show prominent generalization patterns in cerebellar learning. Since the known function of cerebellum is rapidly expanding from pure motor control to domains that include cognition, reward-learning, fear-learning, social function, and even addiction, our data implies generalization controlled by cerebellum in all these domains.Significance StatementConditioned stimuli that resemble each other will evoke a rather similar behavioral response. Here, we investigate this phenomenon of stimulus generalization using Pavlovian eyeblink conditioning to probe cerebellar function. Cerebellum is a brain structure whose known function is rapidly expanding from pure motor control to domains that include cognition, reward-learning, fear-learning, social function, and even addiction. Since we found a strong generalization of the auditory stimulus in eyeblink conditioning, our data implies an important role for generalization in motor and non-moto

Published
2022

36. Proposal of 0.5 mg of protein/100 g of processed food as threshold for voluntary declaration of food allergen traces in processed food-A first step in an initiative to better inform patients and avoid fatal allergic reactions : A GA(2)LEN position paper

Author

Zuberbier, Torsten, Doerr, Tamara, Aberer, Werner, Alvaro, Montserrat, Angier, Elizabeth, Arasi, Stefania, Arshad, Hasan, Ballmer-Weber, Barbara, Bartra, Joan, Beck, Lisa, Begin, Philippe, Bindslev-Jensen, Carsten, Bislimovska, Jovanka, Bousquet, Jean, Brockow, Knut, Bush, Andrew, Cianferoni, Antonella, Cork, Michael J., Custovic, Adnan, Darsow, Ulf, Jong, Nicolette, Deleanu, Diana, Del Giacco, Stefano, Deschildre, Antoine, Galvin, Audrey Dunn, Ebisawa, Motohiro, Fernandez-Rivas, Montserrat, Ferrer, Marta, Fiocchi, Alessandro, van Wijk, Roy Gerth, Gotua, Maia, Grimshaw, Kate, Gruenhagen, Josefine, Heffler, Enrico, Hide, Michihiro, Hoffmann-Sommergruber, Karin, Incorvaia, Cristoforo, Janson, Christer, John, Swen Malte, Jones, Carla, Jutel, Marek, Katoh, Norito, Kendziora, Benjamin, Kinaciyan, Tamar, Knol, Edward, Kurbacheva, Oksana, Lau, Susanne, Loh, Richard, Lombardi, Carlo, Makela, Mika, Marchisotto, Mary Jane, Makris, Michael, Maurer, Marcus, Meyer, Rosan, Mijakoski, Dragan, Minov, Jordan, Mullol, Joaquim, Nilsson, Caroline, Nowak-Wegrzyn, Anna, Nwaru, Bright, I, Odemyr, Mikela, Pajno, Giovanni Battista, Paudel, Sushil, Papadopoulos, Nikolaos G., Renz, Harald, Ricci, Giampaolo, Ring, Johannes, Rogala, Barbara, Sampson, Hugh, Senna, Gianenrico, Sitkauskiene, Brigita, Smith, Peter Kenneth, Stevanovic, Katarina, Stoleski, Sasho, Szajewska, Hania, Tanaka, Akio, Todo-Bom, Ana, Topal, Fatih Alexander, Valovirta, Erkka, Van Ree, Ronald, Venter, Carina, Woehrl, Stefan, Wong, Gary W. K., Zhao, Zuotao, Worm, Margitta, Zuberbier, Torsten, Doerr, Tamara, Aberer, Werner, Alvaro, Montserrat, Angier, Elizabeth, Arasi, Stefania, Arshad, Hasan, Ballmer-Weber, Barbara, Bartra, Joan, Beck, Lisa, Begin, Philippe, Bindslev-Jensen, Carsten, Bislimovska, Jovanka, Bousquet, Jean, Brockow, Knut, Bush, Andrew, Cianferoni, Antonella, Cork, Michael J., Custovic, Adnan, Darsow, Ulf, Jong, Nicolette, Deleanu, Diana, Del Giacco, Stefano, Deschildre, Antoine, Galvin, Audrey Dunn, Ebisawa, Motohiro, Fernandez-Rivas, Montserrat, Ferrer, Marta, Fiocchi, Alessandro, van Wijk, Roy Gerth, Gotua, Maia, Grimshaw, Kate, Gruenhagen, Josefine, Heffler, Enrico, Hide, Michihiro, Hoffmann-Sommergruber, Karin, Incorvaia, Cristoforo, Janson, Christer, John, Swen Malte, Jones, Carla, Jutel, Marek, Katoh, Norito, Kendziora, Benjamin, Kinaciyan, Tamar, Knol, Edward, Kurbacheva, Oksana, Lau, Susanne, Loh, Richard, Lombardi, Carlo, Makela, Mika, Marchisotto, Mary Jane, Makris, Michael, Maurer, Marcus, Meyer, Rosan, Mijakoski, Dragan, Minov, Jordan, Mullol, Joaquim, Nilsson, Caroline, Nowak-Wegrzyn, Anna, Nwaru, Bright, I, Odemyr, Mikela, Pajno, Giovanni Battista, Paudel, Sushil, Papadopoulos, Nikolaos G., Renz, Harald, Ricci, Giampaolo, Ring, Johannes, Rogala, Barbara, Sampson, Hugh, Senna, Gianenrico, Sitkauskiene, Brigita, Smith, Peter Kenneth, Stevanovic, Katarina, Stoleski, Sasho, Szajewska, Hania, Tanaka, Akio, Todo-Bom, Ana, Topal, Fatih Alexander, Valovirta, Erkka, Van Ree, Ronald, Venter, Carina, Woehrl, Stefan, Wong, Gary W. K., Zhao, Zuotao, and Worm, Margitta

Abstract

Background Food anaphylaxis is commonly elicited by unintentional ingestion of foods containing the allergen above the tolerance threshold level of the individual. While labeling the 14 main allergens used as ingredients in food products is mandatory in the EU, there is no legal definition of declaring potential contaminants. Precautionary allergen labeling such as "may contain traces of" is often used. However, this is unsatisfactory for consumers as they get no information if the contamination is below their personal threshold. In discussions with the food industry and technologists, it was suggested to use a voluntary declaration indicating that all declared contaminants are below a threshold of 0.5 mg protein per 100 g of food. This concentration is known to be below the threshold of most patients, and it can be technically guaranteed in most food production. However, it was also important to assess that in case of accidental ingestion of contaminants below this threshold by highly allergic patients, no fatal anaphylactic reaction could occur. Therefore, we performed a systematic review to assess whether a fatal reaction to 5mg of protein or less has been reported, assuming that a maximum portion size of 1kg of a processed food exceeds any meal and thus gives a sufficient safety margin. Methods MEDLINE and EMBASE were searched until 24 January 2021 for provocation studies and case reports in which one of the 14 major food allergens was reported to elicit fatal or life-threatening anaphylactic reactions and assessed if these occurred below the ingestion of 5mg of protein. A Delphi process was performed to obtain an expert consensus on the results. Results In the 210 studies included, in our search, no reports of fatal anaphylactic reactions reported below 5 mg protein ingested were identified. However, in provocation studies and case reports, severe reactions below 5 mg were reported for the following allergens: eggs, fish, lupin, milk, nuts, peanuts, soy, and se

Published
2022
Full Text
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37. Proposal of 0.5 mg of protein/100 g of processed food as threshold for voluntary declaration of food allergen traces in processed food-A first step in an initiative to better inform patients and avoid fatal allergic reactions : A GA(2)LEN position paper

Author

Zuberbier, Torsten, Doerr, Tamara, Aberer, Werner, Alvaro, Montserrat, Angier, Elizabeth, Arasi, Stefania, Arshad, Hasan, Ballmer-Weber, Barbara, Bartra, Joan, Beck, Lisa, Begin, Philippe, Bindslev-Jensen, Carsten, Bislimovska, Jovanka, Bousquet, Jean, Brockow, Knut, Bush, Andrew, Cianferoni, Antonella, Cork, Michael J., Custovic, Adnan, Darsow, Ulf, Jong, Nicolette, Deleanu, Diana, Del Giacco, Stefano, Deschildre, Antoine, Galvin, Audrey Dunn, Ebisawa, Motohiro, Fernandez-Rivas, Montserrat, Ferrer, Marta, Fiocchi, Alessandro, van Wijk, Roy Gerth, Gotua, Maia, Grimshaw, Kate, Gruenhagen, Josefine, Heffler, Enrico, Hide, Michihiro, Hoffmann-Sommergruber, Karin, Incorvaia, Cristoforo, Janson, Christer, John, Swen Malte, Jones, Carla, Jutel, Marek, Katoh, Norito, Kendziora, Benjamin, Kinaciyan, Tamar, Knol, Edward, Kurbacheva, Oksana, Lau, Susanne, Loh, Richard, Lombardi, Carlo, Makela, Mika, Marchisotto, Mary Jane, Makris, Michael, Maurer, Marcus, Meyer, Rosan, Mijakoski, Dragan, Minov, Jordan, Mullol, Joaquim, Nilsson, Caroline, Nowak-Wegrzyn, Anna, Nwaru, Bright, I, Odemyr, Mikela, Pajno, Giovanni Battista, Paudel, Sushil, Papadopoulos, Nikolaos G., Renz, Harald, Ricci, Giampaolo, Ring, Johannes, Rogala, Barbara, Sampson, Hugh, Senna, Gianenrico, Sitkauskiene, Brigita, Smith, Peter Kenneth, Stevanovic, Katarina, Stoleski, Sasho, Szajewska, Hania, Tanaka, Akio, Todo-Bom, Ana, Topal, Fatih Alexander, Valovirta, Erkka, Van Ree, Ronald, Venter, Carina, Woehrl, Stefan, Wong, Gary W. K., Zhao, Zuotao, Worm, Margitta, Zuberbier, Torsten, Doerr, Tamara, Aberer, Werner, Alvaro, Montserrat, Angier, Elizabeth, Arasi, Stefania, Arshad, Hasan, Ballmer-Weber, Barbara, Bartra, Joan, Beck, Lisa, Begin, Philippe, Bindslev-Jensen, Carsten, Bislimovska, Jovanka, Bousquet, Jean, Brockow, Knut, Bush, Andrew, Cianferoni, Antonella, Cork, Michael J., Custovic, Adnan, Darsow, Ulf, Jong, Nicolette, Deleanu, Diana, Del Giacco, Stefano, Deschildre, Antoine, Galvin, Audrey Dunn, Ebisawa, Motohiro, Fernandez-Rivas, Montserrat, Ferrer, Marta, Fiocchi, Alessandro, van Wijk, Roy Gerth, Gotua, Maia, Grimshaw, Kate, Gruenhagen, Josefine, Heffler, Enrico, Hide, Michihiro, Hoffmann-Sommergruber, Karin, Incorvaia, Cristoforo, Janson, Christer, John, Swen Malte, Jones, Carla, Jutel, Marek, Katoh, Norito, Kendziora, Benjamin, Kinaciyan, Tamar, Knol, Edward, Kurbacheva, Oksana, Lau, Susanne, Loh, Richard, Lombardi, Carlo, Makela, Mika, Marchisotto, Mary Jane, Makris, Michael, Maurer, Marcus, Meyer, Rosan, Mijakoski, Dragan, Minov, Jordan, Mullol, Joaquim, Nilsson, Caroline, Nowak-Wegrzyn, Anna, Nwaru, Bright, I, Odemyr, Mikela, Pajno, Giovanni Battista, Paudel, Sushil, Papadopoulos, Nikolaos G., Renz, Harald, Ricci, Giampaolo, Ring, Johannes, Rogala, Barbara, Sampson, Hugh, Senna, Gianenrico, Sitkauskiene, Brigita, Smith, Peter Kenneth, Stevanovic, Katarina, Stoleski, Sasho, Szajewska, Hania, Tanaka, Akio, Todo-Bom, Ana, Topal, Fatih Alexander, Valovirta, Erkka, Van Ree, Ronald, Venter, Carina, Woehrl, Stefan, Wong, Gary W. K., Zhao, Zuotao, and Worm, Margitta

Abstract

Background Food anaphylaxis is commonly elicited by unintentional ingestion of foods containing the allergen above the tolerance threshold level of the individual. While labeling the 14 main allergens used as ingredients in food products is mandatory in the EU, there is no legal definition of declaring potential contaminants. Precautionary allergen labeling such as "may contain traces of" is often used. However, this is unsatisfactory for consumers as they get no information if the contamination is below their personal threshold. In discussions with the food industry and technologists, it was suggested to use a voluntary declaration indicating that all declared contaminants are below a threshold of 0.5 mg protein per 100 g of food. This concentration is known to be below the threshold of most patients, and it can be technically guaranteed in most food production. However, it was also important to assess that in case of accidental ingestion of contaminants below this threshold by highly allergic patients, no fatal anaphylactic reaction could occur. Therefore, we performed a systematic review to assess whether a fatal reaction to 5mg of protein or less has been reported, assuming that a maximum portion size of 1kg of a processed food exceeds any meal and thus gives a sufficient safety margin. Methods MEDLINE and EMBASE were searched until 24 January 2021 for provocation studies and case reports in which one of the 14 major food allergens was reported to elicit fatal or life-threatening anaphylactic reactions and assessed if these occurred below the ingestion of 5mg of protein. A Delphi process was performed to obtain an expert consensus on the results. Results In the 210 studies included, in our search, no reports of fatal anaphylactic reactions reported below 5 mg protein ingested were identified. However, in provocation studies and case reports, severe reactions below 5 mg were reported for the following allergens: eggs, fish, lupin, milk, nuts, peanuts, soy, and se

Published
2022
Full Text
View/download PDF

38. Proposal of 0.5 mg of protein/100 g of processed food as threshold for voluntary declaration of food allergen traces in processed food-A first step in an initiative to better inform patients and avoid fatal allergic reactions : A GA(2)LEN position paper

Author

Zuberbier, Torsten, Doerr, Tamara, Aberer, Werner, Alvaro, Montserrat, Angier, Elizabeth, Arasi, Stefania, Arshad, Hasan, Ballmer-Weber, Barbara, Bartra, Joan, Beck, Lisa, Begin, Philippe, Bindslev-Jensen, Carsten, Bislimovska, Jovanka, Bousquet, Jean, Brockow, Knut, Bush, Andrew, Cianferoni, Antonella, Cork, Michael J., Custovic, Adnan, Darsow, Ulf, Jong, Nicolette, Deleanu, Diana, Del Giacco, Stefano, Deschildre, Antoine, Galvin, Audrey Dunn, Ebisawa, Motohiro, Fernandez-Rivas, Montserrat, Ferrer, Marta, Fiocchi, Alessandro, van Wijk, Roy Gerth, Gotua, Maia, Grimshaw, Kate, Gruenhagen, Josefine, Heffler, Enrico, Hide, Michihiro, Hoffmann-Sommergruber, Karin, Incorvaia, Cristoforo, Janson, Christer, John, Swen Malte, Jones, Carla, Jutel, Marek, Katoh, Norito, Kendziora, Benjamin, Kinaciyan, Tamar, Knol, Edward, Kurbacheva, Oksana, Lau, Susanne, Loh, Richard, Lombardi, Carlo, Makela, Mika, Marchisotto, Mary Jane, Makris, Michael, Maurer, Marcus, Meyer, Rosan, Mijakoski, Dragan, Minov, Jordan, Mullol, Joaquim, Nilsson, Caroline, Nowak-Wegrzyn, Anna, Nwaru, Bright, I, Odemyr, Mikela, Pajno, Giovanni Battista, Paudel, Sushil, Papadopoulos, Nikolaos G., Renz, Harald, Ricci, Giampaolo, Ring, Johannes, Rogala, Barbara, Sampson, Hugh, Senna, Gianenrico, Sitkauskiene, Brigita, Smith, Peter Kenneth, Stevanovic, Katarina, Stoleski, Sasho, Szajewska, Hania, Tanaka, Akio, Todo-Bom, Ana, Topal, Fatih Alexander, Valovirta, Erkka, Van Ree, Ronald, Venter, Carina, Woehrl, Stefan, Wong, Gary W. K., Zhao, Zuotao, Worm, Margitta, Zuberbier, Torsten, Doerr, Tamara, Aberer, Werner, Alvaro, Montserrat, Angier, Elizabeth, Arasi, Stefania, Arshad, Hasan, Ballmer-Weber, Barbara, Bartra, Joan, Beck, Lisa, Begin, Philippe, Bindslev-Jensen, Carsten, Bislimovska, Jovanka, Bousquet, Jean, Brockow, Knut, Bush, Andrew, Cianferoni, Antonella, Cork, Michael J., Custovic, Adnan, Darsow, Ulf, Jong, Nicolette, Deleanu, Diana, Del Giacco, Stefano, Deschildre, Antoine, Galvin, Audrey Dunn, Ebisawa, Motohiro, Fernandez-Rivas, Montserrat, Ferrer, Marta, Fiocchi, Alessandro, van Wijk, Roy Gerth, Gotua, Maia, Grimshaw, Kate, Gruenhagen, Josefine, Heffler, Enrico, Hide, Michihiro, Hoffmann-Sommergruber, Karin, Incorvaia, Cristoforo, Janson, Christer, John, Swen Malte, Jones, Carla, Jutel, Marek, Katoh, Norito, Kendziora, Benjamin, Kinaciyan, Tamar, Knol, Edward, Kurbacheva, Oksana, Lau, Susanne, Loh, Richard, Lombardi, Carlo, Makela, Mika, Marchisotto, Mary Jane, Makris, Michael, Maurer, Marcus, Meyer, Rosan, Mijakoski, Dragan, Minov, Jordan, Mullol, Joaquim, Nilsson, Caroline, Nowak-Wegrzyn, Anna, Nwaru, Bright, I, Odemyr, Mikela, Pajno, Giovanni Battista, Paudel, Sushil, Papadopoulos, Nikolaos G., Renz, Harald, Ricci, Giampaolo, Ring, Johannes, Rogala, Barbara, Sampson, Hugh, Senna, Gianenrico, Sitkauskiene, Brigita, Smith, Peter Kenneth, Stevanovic, Katarina, Stoleski, Sasho, Szajewska, Hania, Tanaka, Akio, Todo-Bom, Ana, Topal, Fatih Alexander, Valovirta, Erkka, Van Ree, Ronald, Venter, Carina, Woehrl, Stefan, Wong, Gary W. K., Zhao, Zuotao, and Worm, Margitta

Abstract

Background Food anaphylaxis is commonly elicited by unintentional ingestion of foods containing the allergen above the tolerance threshold level of the individual. While labeling the 14 main allergens used as ingredients in food products is mandatory in the EU, there is no legal definition of declaring potential contaminants. Precautionary allergen labeling such as "may contain traces of" is often used. However, this is unsatisfactory for consumers as they get no information if the contamination is below their personal threshold. In discussions with the food industry and technologists, it was suggested to use a voluntary declaration indicating that all declared contaminants are below a threshold of 0.5 mg protein per 100 g of food. This concentration is known to be below the threshold of most patients, and it can be technically guaranteed in most food production. However, it was also important to assess that in case of accidental ingestion of contaminants below this threshold by highly allergic patients, no fatal anaphylactic reaction could occur. Therefore, we performed a systematic review to assess whether a fatal reaction to 5mg of protein or less has been reported, assuming that a maximum portion size of 1kg of a processed food exceeds any meal and thus gives a sufficient safety margin. Methods MEDLINE and EMBASE were searched until 24 January 2021 for provocation studies and case reports in which one of the 14 major food allergens was reported to elicit fatal or life-threatening anaphylactic reactions and assessed if these occurred below the ingestion of 5mg of protein. A Delphi process was performed to obtain an expert consensus on the results. Results In the 210 studies included, in our search, no reports of fatal anaphylactic reactions reported below 5 mg protein ingested were identified. However, in provocation studies and case reports, severe reactions below 5 mg were reported for the following allergens: eggs, fish, lupin, milk, nuts, peanuts, soy, and se

Published
2022
Full Text
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39. Micronutritional supplementation with a holoBLG-based FSMP (food for special medical purposes)-lozenge alleviates allergic symptoms in BALB/c mice: Imitating the protective farm effect

Author

Afd Pharmacology, Pharmacology, Afify, Sheriene Moussa, Regner, Andreas, Pacios, Luis F, Blokhuis, Bart R, Jensen, Sebastian A, Redegeld, Frank A, Pali-Schöll, Isabella, Hufnagl, Karin, Bianchini, Rodolfo, Guethoff, Sonja, Kramer, Matthias F, Fiocchi, Alessandro, Dvorak, Zdenek, Jensen-Jarolim, Erika, Roth-Walter, Franziska, Afd Pharmacology, Pharmacology, Afify, Sheriene Moussa, Regner, Andreas, Pacios, Luis F, Blokhuis, Bart R, Jensen, Sebastian A, Redegeld, Frank A, Pali-Schöll, Isabella, Hufnagl, Karin, Bianchini, Rodolfo, Guethoff, Sonja, Kramer, Matthias F, Fiocchi, Alessandro, Dvorak, Zdenek, Jensen-Jarolim, Erika, and Roth-Walter, Franziska

Published
2022

40. Proposal of 0.5 mg of protein/100 g of processed food as threshold for voluntary declaration of food allergen traces in processed food-A first step in an initiative to better inform patients and avoid fatal allergic reactions : A GA(2)LEN position paper

Author

Zuberbier, Torsten, Doerr, Tamara, Aberer, Werner, Alvaro, Montserrat, Angier, Elizabeth, Arasi, Stefania, Arshad, Hasan, Ballmer-Weber, Barbara, Bartra, Joan, Beck, Lisa, Begin, Philippe, Bindslev-Jensen, Carsten, Bislimovska, Jovanka, Bousquet, Jean, Brockow, Knut, Bush, Andrew, Cianferoni, Antonella, Cork, Michael J., Custovic, Adnan, Darsow, Ulf, Jong, Nicolette, Deleanu, Diana, Del Giacco, Stefano, Deschildre, Antoine, Galvin, Audrey Dunn, Ebisawa, Motohiro, Fernandez-Rivas, Montserrat, Ferrer, Marta, Fiocchi, Alessandro, van Wijk, Roy Gerth, Gotua, Maia, Grimshaw, Kate, Gruenhagen, Josefine, Heffler, Enrico, Hide, Michihiro, Hoffmann-Sommergruber, Karin, Incorvaia, Cristoforo, Janson, Christer, John, Swen Malte, Jones, Carla, Jutel, Marek, Katoh, Norito, Kendziora, Benjamin, Kinaciyan, Tamar, Knol, Edward, Kurbacheva, Oksana, Lau, Susanne, Loh, Richard, Lombardi, Carlo, Makela, Mika, Marchisotto, Mary Jane, Makris, Michael, Maurer, Marcus, Meyer, Rosan, Mijakoski, Dragan, Minov, Jordan, Mullol, Joaquim, Nilsson, Caroline, Nowak-Wegrzyn, Anna, Nwaru, Bright, I, Odemyr, Mikela, Pajno, Giovanni Battista, Paudel, Sushil, Papadopoulos, Nikolaos G., Renz, Harald, Ricci, Giampaolo, Ring, Johannes, Rogala, Barbara, Sampson, Hugh, Senna, Gianenrico, Sitkauskiene, Brigita, Smith, Peter Kenneth, Stevanovic, Katarina, Stoleski, Sasho, Szajewska, Hania, Tanaka, Akio, Todo-Bom, Ana, Topal, Fatih Alexander, Valovirta, Erkka, Van Ree, Ronald, Venter, Carina, Woehrl, Stefan, Wong, Gary W. K., Zhao, Zuotao, Worm, Margitta, Zuberbier, Torsten, Doerr, Tamara, Aberer, Werner, Alvaro, Montserrat, Angier, Elizabeth, Arasi, Stefania, Arshad, Hasan, Ballmer-Weber, Barbara, Bartra, Joan, Beck, Lisa, Begin, Philippe, Bindslev-Jensen, Carsten, Bislimovska, Jovanka, Bousquet, Jean, Brockow, Knut, Bush, Andrew, Cianferoni, Antonella, Cork, Michael J., Custovic, Adnan, Darsow, Ulf, Jong, Nicolette, Deleanu, Diana, Del Giacco, Stefano, Deschildre, Antoine, Galvin, Audrey Dunn, Ebisawa, Motohiro, Fernandez-Rivas, Montserrat, Ferrer, Marta, Fiocchi, Alessandro, van Wijk, Roy Gerth, Gotua, Maia, Grimshaw, Kate, Gruenhagen, Josefine, Heffler, Enrico, Hide, Michihiro, Hoffmann-Sommergruber, Karin, Incorvaia, Cristoforo, Janson, Christer, John, Swen Malte, Jones, Carla, Jutel, Marek, Katoh, Norito, Kendziora, Benjamin, Kinaciyan, Tamar, Knol, Edward, Kurbacheva, Oksana, Lau, Susanne, Loh, Richard, Lombardi, Carlo, Makela, Mika, Marchisotto, Mary Jane, Makris, Michael, Maurer, Marcus, Meyer, Rosan, Mijakoski, Dragan, Minov, Jordan, Mullol, Joaquim, Nilsson, Caroline, Nowak-Wegrzyn, Anna, Nwaru, Bright, I, Odemyr, Mikela, Pajno, Giovanni Battista, Paudel, Sushil, Papadopoulos, Nikolaos G., Renz, Harald, Ricci, Giampaolo, Ring, Johannes, Rogala, Barbara, Sampson, Hugh, Senna, Gianenrico, Sitkauskiene, Brigita, Smith, Peter Kenneth, Stevanovic, Katarina, Stoleski, Sasho, Szajewska, Hania, Tanaka, Akio, Todo-Bom, Ana, Topal, Fatih Alexander, Valovirta, Erkka, Van Ree, Ronald, Venter, Carina, Woehrl, Stefan, Wong, Gary W. K., Zhao, Zuotao, and Worm, Margitta

Abstract

Background Food anaphylaxis is commonly elicited by unintentional ingestion of foods containing the allergen above the tolerance threshold level of the individual. While labeling the 14 main allergens used as ingredients in food products is mandatory in the EU, there is no legal definition of declaring potential contaminants. Precautionary allergen labeling such as "may contain traces of" is often used. However, this is unsatisfactory for consumers as they get no information if the contamination is below their personal threshold. In discussions with the food industry and technologists, it was suggested to use a voluntary declaration indicating that all declared contaminants are below a threshold of 0.5 mg protein per 100 g of food. This concentration is known to be below the threshold of most patients, and it can be technically guaranteed in most food production. However, it was also important to assess that in case of accidental ingestion of contaminants below this threshold by highly allergic patients, no fatal anaphylactic reaction could occur. Therefore, we performed a systematic review to assess whether a fatal reaction to 5mg of protein or less has been reported, assuming that a maximum portion size of 1kg of a processed food exceeds any meal and thus gives a sufficient safety margin. Methods MEDLINE and EMBASE were searched until 24 January 2021 for provocation studies and case reports in which one of the 14 major food allergens was reported to elicit fatal or life-threatening anaphylactic reactions and assessed if these occurred below the ingestion of 5mg of protein. A Delphi process was performed to obtain an expert consensus on the results. Results In the 210 studies included, in our search, no reports of fatal anaphylactic reactions reported below 5 mg protein ingested were identified. However, in provocation studies and case reports, severe reactions below 5 mg were reported for the following allergens: eggs, fish, lupin, milk, nuts, peanuts, soy, and se

Published
2022
Full Text
View/download PDF

41. Real-world data using mHealth apps in rhinitis, rhinosinusitis and their multimorbidities

Author

Sousa-Pinto, Bernardo, Anto, Aram, Berger, Markus, Dramburg, Stephanie, Pfaar, Oliver, Klimek, Ludger, Jutel, Marek, Czarlewski, Wienczyslawa, Bedbrook, Anna, Valiulis, Arunas, Agache, Ioana, Amaral, Rita, Ansotegui, Ignacio J., Bastl, Katharina, Berger, Uwe, Bergmann, Karl C., Bosnic-Anticevich, Sinthia, Braido, Fulvio, Brussino, Luisa, Cardona, Victoria, Casale, Thomas, Canonica, G. Walter, Cecchi, Lorenzo, Charpin, Denis, Chivato, Tomás, Chu, Derek K., Cingi, Cemal, Costa, Elisio M., Cruz, Alvaro A., Devillier, Philippe, Durham, Stephen R., Ebisawa, Motohiro, Fiocchi, Alessandro, Fokkens, Wytske J., Gemicioğlu, Bilun, Gotua, Maia, Guzmán, Maria Antonieta, Haahtela, Tari, Ivancevich, Juan Carlos, Kuna, Piotr, Kaidashev, Igor, Khaitov, Musa, Kvedariene, Violeta, Larenas-Linnemann, Désirée E., Lipworth, Brian, Laune, Daniel, Matricardi, Paolo M., Morais-Almeida, Mario, Mullol, Joaquim, Naclerio, Robert, Neffen, Hugo, Nekam, Kristoff, Niedoszytko, Marek, Okamoto, Yoshitaka, Papadopoulos, Nikolaos G., Park, Hae Sim, Passalacqua, Giovanni, Patella, Vincenzo, Pelosi, Simone, Pham-Thi, Nhân, Popov, Ted A., Regateiro, Frederico S., Reitsma, Sietze, Rodriguez-Gonzales, Monica, Rosario, Nelson, Rouadi, Philip W., Samolinski, Boleslaw, Sá-Sousa, Ana, Sastre, Joaquin, Sheikh, Aziz, Ulrik, Charlotte Suppli, Taborda-Barata, Luis, Todo-Bom, Ana, Tomazic, Peter Valentin, Toppila-Salmi, Sanna, Tripodi, Salvatore, Tsiligianni, Ioanna, Valovirta, Erkka, Ventura, Maria Teresa, Valero, Antonio A., Vieira, Rafael José, Wallace, Dana, Waserman, Susan, Williams, Sian, Yorgancioglu, Arzu, Zhang, Luo, Zidarn, Mihaela, Zuberbier, Jaron, Olze, Heidi, Antó, Josep M., Zuberbier, Torsten, Fonseca, João A., Bousquet, Jean, Sousa-Pinto, Bernardo, Anto, Aram, Berger, Markus, Dramburg, Stephanie, Pfaar, Oliver, Klimek, Ludger, Jutel, Marek, Czarlewski, Wienczyslawa, Bedbrook, Anna, Valiulis, Arunas, Agache, Ioana, Amaral, Rita, Ansotegui, Ignacio J., Bastl, Katharina, Berger, Uwe, Bergmann, Karl C., Bosnic-Anticevich, Sinthia, Braido, Fulvio, Brussino, Luisa, Cardona, Victoria, Casale, Thomas, Canonica, G. Walter, Cecchi, Lorenzo, Charpin, Denis, Chivato, Tomás, Chu, Derek K., Cingi, Cemal, Costa, Elisio M., Cruz, Alvaro A., Devillier, Philippe, Durham, Stephen R., Ebisawa, Motohiro, Fiocchi, Alessandro, Fokkens, Wytske J., Gemicioğlu, Bilun, Gotua, Maia, Guzmán, Maria Antonieta, Haahtela, Tari, Ivancevich, Juan Carlos, Kuna, Piotr, Kaidashev, Igor, Khaitov, Musa, Kvedariene, Violeta, Larenas-Linnemann, Désirée E., Lipworth, Brian, Laune, Daniel, Matricardi, Paolo M., Morais-Almeida, Mario, Mullol, Joaquim, Naclerio, Robert, Neffen, Hugo, Nekam, Kristoff, Niedoszytko, Marek, Okamoto, Yoshitaka, Papadopoulos, Nikolaos G., Park, Hae Sim, Passalacqua, Giovanni, Patella, Vincenzo, Pelosi, Simone, Pham-Thi, Nhân, Popov, Ted A., Regateiro, Frederico S., Reitsma, Sietze, Rodriguez-Gonzales, Monica, Rosario, Nelson, Rouadi, Philip W., Samolinski, Boleslaw, Sá-Sousa, Ana, Sastre, Joaquin, Sheikh, Aziz, Ulrik, Charlotte Suppli, Taborda-Barata, Luis, Todo-Bom, Ana, Tomazic, Peter Valentin, Toppila-Salmi, Sanna, Tripodi, Salvatore, Tsiligianni, Ioanna, Valovirta, Erkka, Ventura, Maria Teresa, Valero, Antonio A., Vieira, Rafael José, Wallace, Dana, Waserman, Susan, Williams, Sian, Yorgancioglu, Arzu, Zhang, Luo, Zidarn, Mihaela, Zuberbier, Jaron, Olze, Heidi, Antó, Josep M., Zuberbier, Torsten, Fonseca, João A., and Bousquet, Jean

Abstract

Digital health is an umbrella term which encompasses eHealth and benefits from areas such as advanced computer sciences. eHealth includes mHealth apps, which offer the potential to redesign aspects of healthcare delivery. The capacity of apps to collect large amounts of longitudinal, real-time, real-world data enables the progression of biomedical knowledge. Apps for rhinitis and rhinosinusitis were searched for in the Google Play and Apple App stores, via an automatic market research tool recently developed using JavaScript. Over 1500 apps for allergic rhinitis and rhinosinusitis were identified, some dealing with multimorbidity. However, only six apps for rhinitis (AirRater, AllergyMonitor, AllerSearch, Husteblume, MASK-air and Pollen App) and one for rhinosinusitis (Galenus Health) have so far published results in the scientific literature. These apps were reviewed for their validation, discovery of novel allergy phenotypes, optimisation of identifying the pollen season, novel approaches in diagnosis and management (pharmacotherapy and allergen immunotherapy) as well as adherence to treatment. Published evidence demonstrates the potential of mobile health apps to advance in the characterisation, diagnosis and management of rhinitis and rhinosinusitis patients.

Published
2022

42. An inflammatory Signature of Glucose Impairment in Cystic Fibrosis

Author

Montemari,Anna Lisa, Manco,Melania, Fiocchi,Alessandro Giovanni, Bartoli,Manuela, Facchiano,Francesco, Tabolacci,Claudio, Scatigna,Maria, Ciciriello,Fabiana, Alghisi,Federico, Montemitro,Enza, Carsetti,Rita, Lucidi,Vincenzina, Fiscarelli,Ersilia Vita, Montemari,Anna Lisa, Manco,Melania, Fiocchi,Alessandro Giovanni, Bartoli,Manuela, Facchiano,Francesco, Tabolacci,Claudio, Scatigna,Maria, Ciciriello,Fabiana, Alghisi,Federico, Montemitro,Enza, Carsetti,Rita, Lucidi,Vincenzina, and Fiscarelli,Ersilia Vita

Abstract

Anna Lisa Montemari,1 Melania Manco,2 Alessandro Giovanni Fiocchi,3 Manuela Bartoli,4 Francesco Facchiano,5 Claudio Tabolacci,5 Maria Scatigna,6 Fabiana Ciciriello,3 Federico Alghisi,3 Enza Montemitro,3 Rita Carsetti,7 Vincenzina Lucidi,3 Ersilia Vita Fiscarelli1 1UOS Cystic Fibrosis Diagnostic, UOC Microbiology and Immunology Diagnostic, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy; 2Research Area for Multifactorial Diseases, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy; 3Cystic Fibrosis Unit, Department of Pediatrics Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy; 4Department of Ophthalmology, Medical College of Georgia, Augusta University, Augusta, GA, USA; 5Department of Oncology and Molecular Medicine, Istituto Superiore Di Sanità, Rome, Italy; 6Department of Life, Health and Environmental Sciences, University of L’Aquila, L’Aquila, Italy; 7Diagnostic Immunology Unit, Department of Laboratories, B Cell Pathophysiology Unit, Immunology Research Area, Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyCorrespondence: Melania Manco, Bambino Gesù Children’s Hospital, IRCCS, piazza Sant’Onofrio 4, Rome, Italy, Tel +39 06 6859 2649, Fax +39 06 6859 2904, Email melania.manco@opbg.netObjective and Design: Cystic fibrosis-related diabetes (CFRD) is a severe complication associated with increased morbidity and mortality in cystic fibrosis (CF) patients. Extensive inflammatory state in CF leads to pancreas damage and insulin resistance with consequent altered glucose tolerance and CFRD development. The aim of the present study was to identify circulating levels of inflammatory markers specifically associated with impaired glucose tolerance (IGT) and overt CFRD in a sample of young adults with CF.Materials and Methods: Sixty-four CF outpatients, without evident active pulmonary exacerbation, infectious and

Published
2022

43. Uma obra (in)consequente: a Vala da Azambuja em meados do século XIX

Author

Brandão, José M., Fiocchi Malaspina, Elisabetta, Brandão, José M., and Fiocchi Malaspina, Elisabetta

Abstract

This paper contextualises the foundation of the so-called Companhia dos Canais da Azambuja (1844). The Portuguese government contracted with the Companhia in order to carry out work aimed at making the “vala da Azambuja” navigable throughout the year, extending it to the Onias of Santarém, where a new connection with the Tagus would be opened. According to the original plans of the Dutch engineers Ortts, the works, directed by Mouzinho de Albuquerque and later by the Italian Giulio Sarti, should also contemplate the drainage of rainwater and floods that accumulated in the adjacent fields and guarantee their irrigation during the hot season. Three objectives that were difficult to reconcile in practice, as it turned out, particularly at a time when the country was undergoing major political and economic destabilisation., Este texto contextualiza a criação e os trabalhos da Companhia dos Canais da Azambuja (1844), com a qual o governo contratou a realização de trabalhos visando tornar a “vala da Azambuja” navegável durante todo o ano, ampliando-a até às Onias de Santarém, onde seria aberta uma nova ligação com o Tejo. Segundo os planos originais dos engenheiros holandeses Ortts, os trabalhos dirigidos por Mouzinho de Albuquerque e depois pelo milanês Giulio Sarti, deveriam contemplar também, a drenagem das águas das chuvas e das cheias que se acumulavam nos campos adjacentes e garantir a sua irrigação na estação quente. Três objetivos de difícil conciliação prática, como se verificou, em particular numa época em que o país conheceria uma grande destabilização política e económica.

Published
2022

44. Micronutritional supplementation with a holoBLG-based FSMP (food for special medical purposes)-lozenge alleviates allergic symptoms in BALB/c mice: Imitating the protective farm effect

Author

Afd Pharmacology, Pharmacology, Afify, Sheriene Moussa, Regner, Andreas, Pacios, Luis F, Blokhuis, Bart R, Jensen, Sebastian A, Redegeld, Frank A, Pali-Schöll, Isabella, Hufnagl, Karin, Bianchini, Rodolfo, Guethoff, Sonja, Kramer, Matthias F, Fiocchi, Alessandro, Dvorak, Zdenek, Jensen-Jarolim, Erika, Roth-Walter, Franziska, Afd Pharmacology, Pharmacology, Afify, Sheriene Moussa, Regner, Andreas, Pacios, Luis F, Blokhuis, Bart R, Jensen, Sebastian A, Redegeld, Frank A, Pali-Schöll, Isabella, Hufnagl, Karin, Bianchini, Rodolfo, Guethoff, Sonja, Kramer, Matthias F, Fiocchi, Alessandro, Dvorak, Zdenek, Jensen-Jarolim, Erika, and Roth-Walter, Franziska

Published
2022

45. Stimulus Generalization in Mice during Pavlovian Eyeblink Conditioning

Author

Fiocchi, F. R., Dijkhuizen, S., Koekkoek, S. K.E., De Zeeuw, C. I., Boele, H. J., Fiocchi, F. R., Dijkhuizen, S., Koekkoek, S. K.E., De Zeeuw, C. I., and Boele, H. J.

Abstract

Here, we investigate stimulus generalization in a cerebellar learning paradigm, called eyeblink conditioning. Mice were conditioned to close their eyes in response to a 10-kHz tone by repeatedly pairing this tone with an air puff to the eye 250 ms after tone onset. After 10 consecutive days of training, when mice showed reliable conditioned eyelid responses to the 10-kHz tone, we started to expose them to tones with other frequencies, ranging from 2 to 20 kHz. We found that mice had a strong generalization gradient, whereby the probability and amplitude of conditioned eyelid responses gradually decreases depending on the dissimilarity with the 10-kHz tone. Tones with frequencies closest to 10 kHz evoked the most and largest conditioned eyelid responses and each step away from the 10-kHz tone resulted in fewer and smaller conditioned responses (CRs). In addition, we found that tones with lower frequencies resulted in CRs that peaked earlier after tone onset compared with those to tones with higher frequencies. Together, our data show prominent generalization patterns in cerebellar learning. Since the known function of cerebellum is rapidly expanding from pure motor control to domains that include cognition, reward-learning, fear-learning, social function, and even ad-diction, our data imply generalization controlled by cerebellum in all these domains.

Published
2022

47. Law of persons

Author

Thommen, Marc; https://orcid.org/0000-0001-6816-0738, Thommen, M ( Marc ), Fiocchi Malaspina, Elisabetta, Rossi, Giulia, Thommen, Marc; https://orcid.org/0000-0001-6816-0738, Thommen, M ( Marc ), Fiocchi Malaspina, Elisabetta, and Rossi, Giulia

Published
2022

48. Theratyping of the Rare CFTR Variants E193K and R334W in Rectal Organoid-Derived Epithelial Monolayers

Author

Ciciriello, Fabiana, Bijvelds, Marcel J.C., Alghisi, Federico, Meijsen, Kelly F., Cristiani, Luca, Sorio, Claudio, Melotti, Paola, Fiocchi, Alessandro G., Lucidi, Vincenzina, De Jonge, Hugo R., Ciciriello, Fabiana, Bijvelds, Marcel J.C., Alghisi, Federico, Meijsen, Kelly F., Cristiani, Luca, Sorio, Claudio, Melotti, Paola, Fiocchi, Alessandro G., Lucidi, Vincenzina, and De Jonge, Hugo R.

Abstract

Background: The effect of presently available CFTR modulator combinations, such as elexacaftor (ELX), tezacaftor (TEZ), and ivacaftor (IVA), on rare CFTR alleles is often unknown. Several assays have been developed, such as forskolin-induced swelling (FIS), to evaluate the rescue of such uncommon CFTR alleles both by established and novel modulators in patient-derived primary cell cultures (organoids). Presently, we assessed the CFTR-mediated electrical current across rectal organoid-derived epithelial monolayers. This technique, which allows separate measurement of CFTR-dependent chloride or bicarbonate transport, was used to assess the effect of ELX/TEZ/IVA on two rare CFTR variants. Methods: Intestinal organoid cultures were established from rectal biopsies of CF patients carrying the rare missense mutations E193K or R334W paired with F508del. The effect of the CFTR modulator combination ELX/TEZ/IVA on CFTR-mediated Cl− and HCO3− secretion was assessed in organoid-derived intestinal epithelial monolayers. Non-CF organoids were used for comparison. Clinical biomarkers (sweat chloride, FEV1) were monitored in patients receiving modulator therapy. Results: ELX/TEZ/IVA markedly enhanced CFTR-mediated bicarbonate and chloride transport across intestinal epithelium of both patients. Consistent with the rescue of CFTR function in cultured intestinal cells, ELX/TEZ/IVA therapy improved biomarkers of CFTR function in the R334W/F508del patient. Conclusions: Current measurements in organoid-derived intestinal monolayers can readily be used to monitor CFTR-dependent epithelial Cl− and HCO3− transport. This technique can be explored to assess the functional consequences of rare CFTR mutations and the efficacy of CFTR modulators. We propose that this functional CFTR assay may guide personalized medicine in patients with CF-like clinical manifestations as well as in those carrying rare CFTR mutations.

Published
2022

49. Periostin: Only a tissue biomarker in eosinophilic esophagitis assessment?

Author

Urbani, Sara, Nucera, Eleonora, Fiocchi, Alessandro Giovanni, Mennini, Maurizio, Nucera, Eleonora (ORCID:0000-0002-0565-7680), Urbani, Sara, Nucera, Eleonora, Fiocchi, Alessandro Giovanni, Mennini, Maurizio, and Nucera, Eleonora (ORCID:0000-0002-0565-7680)

Abstract

We read with great interest the article by Muir et al1 in the Journal of Allergy and Clinical Immunology. By using the Esophageal String Test (EST), Muir et al1 highlight the key role of endoluminal periostin (POSTN) in tissue remodeling and fibrosis development in eosinophilic esophagitis (EoE). POSTN detection through EST seems to be a valuable alternative to invasive endoscopy; nevertheless, routinely adopting EST in the clinical care setting remains challenging.

Published
2022

50. Real-world data using mHealth apps in rhinitis, rhinosinusitis and their multimorbidities

Author

Sousa-Pinto, Bernardo, Anto, Aram, Berger, Markus, Dramburg, Stephanie, Pfaar, Oliver, Klimek, Ludger, Jutel, Marek, Czarlewski, Wienczyslawa, Bedbrook, Anna, Valiulis, Arunas, Agache, Ioana, Amaral, Rita, Ansotegui, Ignacio J., Bastl, Katharina, Berger, Uwe, Bergmann, Karl C., Bosnic-Anticevich, Sinthia, Braido, Fulvio, Brussino, Luisa, Cardona, Victoria, Casale, Thomas, Canonica, G. Walter, Cecchi, Lorenzo, Charpin, Denis, Chivato, Tomás, Chu, Derek K., Cingi, Cemal, Costa, Elisio M., Cruz, Alvaro A., Devillier, Philippe, Durham, Stephen R., Ebisawa, Motohiro, Fiocchi, Alessandro, Fokkens, Wytske J., Gemicioğlu, Bilun, Gotua, Maia, Guzmán, Maria Antonieta, Haahtela, Tari, Ivancevich, Juan Carlos, Kuna, Piotr, Kaidashev, Igor, Khaitov, Musa, Kvedariene, Violeta, Larenas-Linnemann, Désirée E., Lipworth, Brian, Laune, Daniel, Matricardi, Paolo M., Morais-Almeida, Mario, Mullol, Joaquim, Naclerio, Robert, Neffen, Hugo, Nekam, Kristoff, Niedoszytko, Marek, Okamoto, Yoshitaka, Papadopoulos, Nikolaos G., Park, Hae Sim, Passalacqua, Giovanni, Patella, Vincenzo, Pelosi, Simone, Pham-Thi, Nhân, Popov, Ted A., Regateiro, Frederico S., Reitsma, Sietze, Rodriguez-Gonzales, Monica, Rosario, Nelson, Rouadi, Philip W., Samolinski, Boleslaw, Sá-Sousa, Ana, Sastre, Joaquin, Sheikh, Aziz, Ulrik, Charlotte Suppli, Taborda-Barata, Luis, Todo-Bom, Ana, Tomazic, Peter Valentin, Toppila-Salmi, Sanna, Tripodi, Salvatore, Tsiligianni, Ioanna, Valovirta, Erkka, Ventura, Maria Teresa, Valero, Antonio A., Vieira, Rafael José, Wallace, Dana, Waserman, Susan, Williams, Sian, Yorgancioglu, Arzu, Zhang, Luo, Zidarn, Mihaela, Zuberbier, Jaron, Olze, Heidi, Antó, Josep M., Zuberbier, Torsten, Fonseca, João A., Bousquet, Jean, Sousa-Pinto, Bernardo, Anto, Aram, Berger, Markus, Dramburg, Stephanie, Pfaar, Oliver, Klimek, Ludger, Jutel, Marek, Czarlewski, Wienczyslawa, Bedbrook, Anna, Valiulis, Arunas, Agache, Ioana, Amaral, Rita, Ansotegui, Ignacio J., Bastl, Katharina, Berger, Uwe, Bergmann, Karl C., Bosnic-Anticevich, Sinthia, Braido, Fulvio, Brussino, Luisa, Cardona, Victoria, Casale, Thomas, Canonica, G. Walter, Cecchi, Lorenzo, Charpin, Denis, Chivato, Tomás, Chu, Derek K., Cingi, Cemal, Costa, Elisio M., Cruz, Alvaro A., Devillier, Philippe, Durham, Stephen R., Ebisawa, Motohiro, Fiocchi, Alessandro, Fokkens, Wytske J., Gemicioğlu, Bilun, Gotua, Maia, Guzmán, Maria Antonieta, Haahtela, Tari, Ivancevich, Juan Carlos, Kuna, Piotr, Kaidashev, Igor, Khaitov, Musa, Kvedariene, Violeta, Larenas-Linnemann, Désirée E., Lipworth, Brian, Laune, Daniel, Matricardi, Paolo M., Morais-Almeida, Mario, Mullol, Joaquim, Naclerio, Robert, Neffen, Hugo, Nekam, Kristoff, Niedoszytko, Marek, Okamoto, Yoshitaka, Papadopoulos, Nikolaos G., Park, Hae Sim, Passalacqua, Giovanni, Patella, Vincenzo, Pelosi, Simone, Pham-Thi, Nhân, Popov, Ted A., Regateiro, Frederico S., Reitsma, Sietze, Rodriguez-Gonzales, Monica, Rosario, Nelson, Rouadi, Philip W., Samolinski, Boleslaw, Sá-Sousa, Ana, Sastre, Joaquin, Sheikh, Aziz, Ulrik, Charlotte Suppli, Taborda-Barata, Luis, Todo-Bom, Ana, Tomazic, Peter Valentin, Toppila-Salmi, Sanna, Tripodi, Salvatore, Tsiligianni, Ioanna, Valovirta, Erkka, Ventura, Maria Teresa, Valero, Antonio A., Vieira, Rafael José, Wallace, Dana, Waserman, Susan, Williams, Sian, Yorgancioglu, Arzu, Zhang, Luo, Zidarn, Mihaela, Zuberbier, Jaron, Olze, Heidi, Antó, Josep M., Zuberbier, Torsten, Fonseca, João A., and Bousquet, Jean

Abstract

Digital health is an umbrella term which encompasses eHealth and benefits from areas such as advanced computer sciences. eHealth includes mHealth apps, which offer the potential to redesign aspects of healthcare delivery. The capacity of apps to collect large amounts of longitudinal, real-time, real-world data enables the progression of biomedical knowledge. Apps for rhinitis and rhinosinusitis were searched for in the Google Play and Apple App stores, via an automatic market research tool recently developed using JavaScript. Over 1500 apps for allergic rhinitis and rhinosinusitis were identified, some dealing with multimorbidity. However, only six apps for rhinitis (AirRater, AllergyMonitor, AllerSearch, Husteblume, MASK-air and Pollen App) and one for rhinosinusitis (Galenus Health) have so far published results in the scientific literature. These apps were reviewed for their validation, discovery of novel allergy phenotypes, optimisation of identifying the pollen season, novel approaches in diagnosis and management (pharmacotherapy and allergen immunotherapy) as well as adherence to treatment. Published evidence demonstrates the potential of mobile health apps to advance in the characterisation, diagnosis and management of rhinitis and rhinosinusitis patients.

Published
2022

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