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1. Review and standard operating procedures for collection of biospecimens and analysis of biomarkers in new onset refractory status epilepticus.

Author: Hanin, Aurélie, Cespedes, Jorge, Pulluru, Yashwanth, Gopaul, Margaret, Aronica, Eleonora, Decampo, Danielle, Helbig, Ingo, Howe, Charles, Huttner, Anita, Koh, Sookyong, Navarro, Vincent, Taraschenko, Olga, Vezzani, Annamaria, Wilson, Michael, Xian, Julie, Gaspard, Nicolas, and Hirsch, Lawrence
Subjects: biomarkers, biospecimens, new onset refractory status epilepticus, standard operating procedures, Humans, Biological Specimen Banks, Status Epilepticus, Seizures, Drug Resistant Epilepsy, Encephalitis, Biomarkers
Abstract: New onset refractory status epilepticus (NORSE), including its subtype with a preceding febrile illness known as febrile infection-related epilepsy syndrome (FIRES), is one of the most severe forms of status epilepticus. The exact causes of NORSE are currently unknown, and there is so far no disease-specific therapy. Identifying the underlying pathophysiology and discovering specific biomarkers, whether immunologic, infectious, genetic, or other, may help physicians in the management of patients with NORSE. A broad spectrum of biomarkers has been proposed for status epilepticus patients, some of which were evaluated for patients with NORSE. Nonetheless, none has been validated, due to significant variabilities in study cohorts, collected biospecimens, applied analytical methods, and defined outcome endpoints, and to small sample sizes. The NORSE Institute established an open NORSE/FIRES biorepository for health-related data and biological samples allowing the collection of biospecimens worldwide, promoting multicenter research and sharing of data and specimens. Here, we suggest standard operating procedures for biospecimen collection and biobanking in this rare condition. We also propose criteria for the appropriate use of previously collected biospecimens. We predict that the widespread use of standardized procedures will reduce heterogeneity, facilitate the future identification of validated biomarkers for NORSE, and provide a better understanding of the pathophysiology and best clinical management for these patients.
Published: 2023

2. A team science approach to discover novel targets for infantile spasms (IS)

Author: Vezzani, Annamaria, Berg, Anne T, Lowenstein, Daniel H, Klitgaard, Henrik, Goodkin, Howard P, Rho, Jong M, Katsarou, Anna Maria, Pirone, Antonella, Galanopoulou, Aristea S, Dulla, Chris, Nordli, Douglas R, Iacobas, Dumitru A, Sherr, Elliott, Cloyd, James, Veliskova, Jana, Noebels, Jeff L, Millichap, John J, Swann, John W, Koh, Sookyung, Velisek, Libor, Coles, Lisa, Patel, Manisha, Siehr, Meagan S, Jacob, Michele, Seo, Ryan, Heischmann, Svenja, Moshe, Solomon L, Chachua, Tamar, Brima, Tufikameni, Mowrey, Wenzhu B, White, H Steve, Milder, Julie, Lubbers, Laura, and Iyengar, Sloka S
Subjects: Neurosciences, Brain Disorders, Neurodegenerative, Epilepsy, Clinical Research, Neurological, Electroencephalography, Humans, Infant, Interdisciplinary Research, Spasms, Infantile, Translational Research, Biomedical, CURE Infantile Spasms Consortium, CURE Staff, Citizens United for Research in Epilepsy, Hypsarhythmia, West syndrome, infantile spasms, team science
Abstract: Infantile spasms (IS) is a devastating epilepsy syndrome that typically begins in the first year of life. Symptoms consist of stereotypical spasms, developmental delay, and electroencephalogram (EEG) that may demonstrate Hypsarhythmia. Current therapeutic approaches are not always effective, and there is no reliable way to predict which patient will respond to therapy. Given this disorder's complexity and the potential impact of a disease-modifying approach, Citizens United for Research in Epilepsy (CURE) employed a "team science" approach to advance the understanding of IS pathology and explore therapeutic modalities that might lead to the development of new ways to potentially prevent spasms and Hypsarhythmia. This approach was a first-of-its-kind collaborative initiative in epilepsy. The IS initiative funded 8 investigative teams over the course of 1-3 years. Projects included the following: discovery on the basic biology of IS, discovery of novel therapeutic targets, cross-validation of targets, discovery of biomarkers, and prognosis and treatment of IS. The combined efforts of a strong investigative team led to numerous advances in understanding the neural pathways underlying IS, testing of small molecules in preclinical models of IS and generated preliminary data on potential biomarkers. Thus far, the initiative has resulted in over 19 publications and subsequent funding for several investigators. Investigators reported that the IS initiative generally affected their research positively due to its collaborative and iterative nature. It also provided a unique opportunity to mentor junior investigators with an interest in translational research. Learnings included the need for a dedicated project manager and more transparent and real-time communication with investigators. The CURE IS initiative represents a unique approach to fund scientific discoveries on epilepsy. It brought together an interdisciplinary group of investigators-who otherwise would not have collaborated-to find transformative therapies for IS. Learnings from this initiative are being utilized for subsequent initiatives at CURE.
Published: 2021

3. Climate change and epilepsy: Insights from clinical and basic science studies

Author: Gulcebi, Medine I, Bartolini, Emanuele, Lee, Omay, Lisgaras, Christos Panagiotis, Onat, Filiz, Mifsud, Janet, Striano, Pasquale, Vezzani, Annamaria, Hildebrand, Michael S, Jimenez-Jimenez, Diego, Junck, Larry, Lewis-Smith, David, Scheffer, Ingrid E, Thijs, Roland D, Zuberi, Sameer M, Blenkinsop, Stephen, Fowler, Hayley J, Foley, Aideen, Sisodiya, Sanjay M, Consortium, on behalf of the EpilepsyClimateChange, Balestrini, Simona, Berkovic, Samuel, Cavalleri, Gianpiero, Correa, Daniel José, Custodio, Helena Martins, Galovic, Marian, Guerrini, Renzo, Henshall, David, Howard, Olga, Hughes, Kelvin, Katsarou, Anna, Koeleman, Bobby PC, Krause, Roland, Lowenstein, Daniel, Mandelenaki, Despoina, Marini, Carla, O'Brien, Terence J, Pace, Adrian, De Palma, Luca, Perucca, Piero, Pitkänen, Asla, Quinn, Finola, Selmer, Kaja Kristine, Steward, Charles A, Swanborough, Nicola, Thijs, Roland, Tittensor, Phil, Trivisano, Marina, Weckhuysen, Sarah, and Zara, Federico
Subjects: Biomedical and Clinical Sciences, Neurosciences, Epilepsy, Climate-Related Exposures and Conditions, Global Warming Climate Change, Brain Disorders, Climate Change, Sleep Research, Neurodegenerative, Aetiology, 2.1 Biological and endogenous factors, Neurological, Climate Action, Animals, COVID-19, Death, Sudden, Global Health, Hot Temperature, Humans, Humidity, Public Health, Sleep Deprivation, Weather, Global warming, Emergency, Seizure, Temperature, Extreme weather events, Public health, Epilepsy Climate Change Consortium, Clinical Sciences, Neurology & Neurosurgery, Biological psychology, Clinical and health psychology
Abstract: Climate change is with us. As professionals who place value on evidence-based practice, climate change is something we cannot ignore. The current pandemic of the novel coronavirus, SARS-CoV-2, has demonstrated how global crises can arise suddenly and have a significant impact on public health. Global warming, a chronic process punctuated by acute episodes of extreme weather events, is an insidious global health crisis needing at least as much attention. Many neurological diseases are complex chronic conditions influenced at many levels by changes in the environment. This review aimed to collate and evaluate reports from clinical and basic science about the relationship between climate change and epilepsy. The keywords climate change, seasonal variation, temperature, humidity, thermoregulation, biorhythm, gene, circadian rhythm, heat, and weather were used to search the published evidence. A number of climatic variables are associated with increased seizure frequency in people with epilepsy. Climate change-induced increase in seizure precipitants such as fevers, stress, and sleep deprivation (e.g. as a result of more frequent extreme weather events) or vector-borne infections may trigger or exacerbate seizures, lead to deterioration of seizure control, and affect neurological, cerebrovascular, or cardiovascular comorbidities and risk of sudden unexpected death in epilepsy. Risks are likely to be modified by many factors, ranging from individual genetic variation and temperature-dependent channel function, to housing quality and global supply chains. According to the results of the limited number of experimental studies with animal models of seizures or epilepsy, different seizure types appear to have distinct susceptibility to seasonal influences. Increased body temperature, whether in the context of fever or not, has a critical role in seizure threshold and seizure-related brain damage. Links between climate change and epilepsy are likely to be multifactorial, complex, and often indirect, which makes predictions difficult. We need more data on possible climate-driven altered risks for seizures, epilepsy, and epileptogenesis, to identify underlying mechanisms at systems, cellular, and molecular levels for better understanding of the impact of climate change on epilepsy. Further focussed data would help us to develop evidence for mitigation methods to do more to protect people with epilepsy from the effects of climate change.
Published: 2021

4. White matter abnormalities across different epilepsy syndromes in adults: an ENIGMA-Epilepsy study

Author: Hatton, Sean N, Huynh, Khoa H, Bonilha, Leonardo, Abela, Eugenio, Alhusaini, Saud, Altmann, Andre, Alvim, Marina KM, Balachandra, Akshara R, Bartolini, Emanuele, Bender, Benjamin, Bernasconi, Neda, Bernasconi, Andrea, Bernhardt, Boris, Bargallo, Núria, Caldairou, Benoit, Caligiuri, Maria E, Carr, Sarah JA, Cavalleri, Gianpiero L, Cendes, Fernando, Concha, Luis, Davoodi-bojd, Esmaeil, Desmond, Patricia M, Devinsky, Orrin, Doherty, Colin P, Domin, Martin, Duncan, John S, Focke, Niels K, Foley, Sonya F, Gambardella, Antonio, Gleichgerrcht, Ezequiel, Guerrini, Renzo, Hamandi, Khalid, Ishikawa, Akari, Keller, Simon S, Kochunov, Peter V, Kotikalapudi, Raviteja, Kreilkamp, Barbara AK, Kwan, Patrick, Labate, Angelo, Langner, Soenke, Lenge, Matteo, Liu, Min, Lui, Elaine, Martin, Pascal, Mascalchi, Mario, Moreira, José CV, Morita-Sherman, Marcia E, O’Brien, Terence J, Pardoe, Heath R, Pariente, José C, Ribeiro, Letícia F, Richardson, Mark P, Rocha, Cristiane S, Rodríguez-Cruces, Raúl, Rosenow, Felix, Severino, Mariasavina, Sinclair, Benjamin, Soltanian-Zadeh, Hamid, Striano, Pasquale, Taylor, Peter N, Thomas, Rhys H, Tortora, Domenico, Velakoulis, Dennis, Vezzani, Annamaria, Vivash, Lucy, von Podewils, Felix, Vos, Sjoerd B, Weber, Bernd, Winston, Gavin P, Yasuda, Clarissa L, Zhu, Alyssa H, Thompson, Paul M, Whelan, Christopher D, Jahanshad, Neda, Sisodiya, Sanjay M, and McDonald, Carrie R
Subjects: Genetics, Neurodegenerative, Epilepsy, Clinical Research, Brain Disorders, Neurosciences, Biomedical Imaging, Aetiology, 2.1 Biological and endogenous factors, Neurological, Adult, Brain, Diffusion Magnetic Resonance Imaging, Epileptic Syndromes, Female, Humans, Image Interpretation, Computer-Assisted, Male, Middle Aged, White Matter, epilepsy, diffusion tensor imaging, multisite analysis, white matter, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery
Abstract: The epilepsies are commonly accompanied by widespread abnormalities in cerebral white matter. ENIGMA-Epilepsy is a large quantitative brain imaging consortium, aggregating data to investigate patterns of neuroimaging abnormalities in common epilepsy syndromes, including temporal lobe epilepsy, extratemporal epilepsy, and genetic generalized epilepsy. Our goal was to rank the most robust white matter microstructural differences across and within syndromes in a multicentre sample of adult epilepsy patients. Diffusion-weighted MRI data were analysed from 1069 healthy controls and 1249 patients: temporal lobe epilepsy with hippocampal sclerosis (n = 599), temporal lobe epilepsy with normal MRI (n = 275), genetic generalized epilepsy (n = 182) and non-lesional extratemporal epilepsy (n = 193). A harmonized protocol using tract-based spatial statistics was used to derive skeletonized maps of fractional anisotropy and mean diffusivity for each participant, and fibre tracts were segmented using a diffusion MRI atlas. Data were harmonized to correct for scanner-specific variations in diffusion measures using a batch-effect correction tool (ComBat). Analyses of covariance, adjusting for age and sex, examined differences between each epilepsy syndrome and controls for each white matter tract (Bonferroni corrected at P
Published: 2020

5. Commonalities in epileptogenic processes from different acute brain insults: Do they translate?

Author: Klein, Pavel, Dingledine, Raymond, Aronica, Eleonora, Bernard, Christophe, Blümcke, Ingmar, Boison, Detlev, Brodie, Martin J, Brooks‐Kayal, Amy R, Engel, Jerome, Forcelli, Patrick A, Hirsch, Lawrence J, Kaminski, Rafal M, Klitgaard, Henrik, Kobow, Katja, Lowenstein, Daniel H, Pearl, Phillip L, Pitkänen, Asla, Puhakka, Noora, Rogawski, Michael A, Schmidt, Dieter, Sillanpää, Matti, Sloviter, Robert S, Steinhäuser, Christian, Vezzani, Annamaria, Walker, Matthew C, and Löscher, Wolfgang
Subjects: Biomedical and Clinical Sciences, Neurosciences, Epilepsy, Neurodegenerative, Prevention, Brain Disorders, Physical Injury - Accidents and Adverse Effects, Traumatic Head and Spine Injury, Aetiology, 2.1 Biological and endogenous factors, Neurological, Animals, Brain Injuries, Disease Models, Animal, Humans, Translational Research, Biomedical, acquired epilepsy, antiepileptogenesis, CNS infections, epileptogenesis, status epilepticus, stroke, traumatic brain injury, Clinical Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract: The most common forms of acquired epilepsies arise following acute brain insults such as traumatic brain injury, stroke, or central nervous system infections. Treatment is effective for only 60%-70% of patients and remains symptomatic despite decades of effort to develop epilepsy prevention therapies. Recent preclinical efforts are focused on likely primary drivers of epileptogenesis, namely inflammation, neuron loss, plasticity, and circuit reorganization. This review suggests a path to identify neuronal and molecular targets for clinical testing of specific hypotheses about epileptogenesis and its prevention or modification. Acquired human epilepsies with different etiologies share some features with animal models. We identify these commonalities and discuss their relevance to the development of successful epilepsy prevention or disease modification strategies. Risk factors for developing epilepsy that appear common to multiple acute injury etiologies include intracranial bleeding, disruption of the blood-brain barrier, more severe injury, and early seizures within 1 week of injury. In diverse human epilepsies and animal models, seizures appear to propagate within a limbic or thalamocortical/corticocortical network. Common histopathologic features of epilepsy of diverse and mostly focal origin are microglial activation and astrogliosis, heterotopic neurons in the white matter, loss of neurons, and the presence of inflammatory cellular infiltrates. Astrocytes exhibit smaller K+ conductances and lose gap junction coupling in many animal models as well as in sclerotic hippocampi from temporal lobe epilepsy patients. There is increasing evidence that epilepsy can be prevented or aborted in preclinical animal models of acquired epilepsy by interfering with processes that appear common to multiple acute injury etiologies, for example, in post-status epilepticus models of focal epilepsy by transient treatment with a trkB/PLCγ1 inhibitor, isoflurane, or HMGB1 antibodies and by topical administration of adenosine, in the cortical fluid percussion injury model by focal cooling, and in the albumin posttraumatic epilepsy model by losartan. Preclinical studies further highlight the roles of mTOR1 pathways, JAK-STAT3, IL-1R/TLR4 signaling, and other inflammatory pathways in the genesis or modulation of epilepsy after brain injury. The wealth of commonalities, diversity of molecular targets identified preclinically, and likely multidimensional nature of epileptogenesis argue for a combinatorial strategy in prevention therapy. Going forward, the identification of impending epilepsy biomarkers to allow better patient selection, together with better alignment with multisite preclinical trials in animal models, should guide the clinical testing of new hypotheses for epileptogenesis and its prevention.
Published: 2018

6. Neuroinflammatory targets and treatments for epilepsy validated in experimental models

Author: Aronica, Eleonora, Bauer, Sebastian, Bozzi, Yuri, Caleo, Matteo, Dingledine, Raymond, Gorter, Jan A, Henshall, David C, Kaufer, Daniela, Koh, Sookyong, Löscher, Wolfgang, Louboutin, Jean‐Pierre, Mishto, Michele, Norwood, Braxton A, Palma, Eleonora, Poulter, Michael O, Terrone, Gaetano, Vezzani, Annamaria, and Kaminski, Rafal M
Subjects: Epilepsy, Biotechnology, Neurosciences, Brain Disorders, Neurodegenerative, 2.1 Biological and endogenous factors, Aetiology, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Neurological, Animals, Anticonvulsants, Brain, Clinical Trials as Topic, Disease Models, Animal, Drug Resistant Epilepsy, Drugs, Investigational, Humans, Neurogenic Inflammation, Inflammation, Immune response, Drug development, Anti-ictogenesis, Antiepileptogenesis, Disease modification, Clinical Sciences, Neurology & Neurosurgery
Abstract: A large body of evidence that has accumulated over the past decade strongly supports the role of inflammation in the pathophysiology of human epilepsy. Specific inflammatory molecules and pathways have been identified that influence various pathologic outcomes in different experimental models of epilepsy. Most importantly, the same inflammatory pathways have also been found in surgically resected brain tissue from patients with treatment-resistant epilepsy. New antiseizure therapies may be derived from these novel potential targets. An essential and crucial question is whether targeting these molecules and pathways may result in anti-ictogenesis, antiepileptogenesis, and/or disease-modification effects. Therefore, preclinical testing in models mimicking relevant aspects of epileptogenesis is needed to guide integrated experimental and clinical trial designs. We discuss the most recent preclinical proof-of-concept studies validating a number of therapeutic approaches against inflammatory mechanisms in animal models that could represent novel avenues for drug development in epilepsy. Finally, we suggest future directions to accelerate preclinical to clinical translation of these recent discoveries.
Published: 2017

7. Epilepsy biomarkers.

Author: Pitkänen, Asla, Loeb, Jeffrey, Dudek, F, Bertram, Edward, Cole, Andrew, Moshé, Solomon, Wiebe, Samuel, Jensen, Frances, Mody, Istvan, Nehlig, Astrid, Vezzani, Annamaria, and Engel, Jerome
Subjects: Biomarkers, Epileptogenesis, Ictogenesis, Surrogate markers, Therapeutic intervention, Animals, Anticonvulsants, Biomarkers, Brain, Clinical Trials as Topic, Cost-Benefit Analysis, Disease Models, Animal, Disease Progression, Drug Discovery, Drug Evaluation, Preclinical, Drug Resistance, Drugs, Investigational, Electroencephalography, Epilepsy, Humans, Precipitating Factors
Abstract: A biomarker is defined as an objectively measured characteristic of a normal or pathologic biologic process. Identification and proper validation of biomarkers of epileptogenesis (the development of epilepsy) and ictogenesis (the propensity to generate spontaneous seizures) might predict the development of an epilepsy condition; identify the presence and severity of tissue capable of generating spontaneous seizures; measure progression after the condition is established; and determine pharmacoresistance. Such biomarkers could be used to create animal models for more cost-effective screening of potential antiepileptogenic and antiseizure drugs and devices, and to reduce the cost of clinical trials by enriching the trial population, and acting as surrogate markers to shorten trial duration. The objectives of the biomarker subgroup for the London Workshop were to define approaches for identifying possible biomarkers for these purposes. Research to identify reliable biomarkers may also reveal underlying mechanisms that could serve as therapeutic targets for the development of new antiepileptogenic and antiseizure compounds.
Published: 2013

8. Epilepsy biomarkers

Author: Engel, Jerome, Pitkänen, Asla, Loeb, Jeffrey A, Dudek, F Edward, Bertram, Edward H, Cole, Andrew J, Moshé, Solomon L, Wiebe, Samuel, Jensen, Frances E, Mody, Istvan, Nehlig, Astrid, and Vezzani, Annamaria
Subjects: Neurosciences, Epilepsy, Neurodegenerative, Brain Disorders, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, Neurological, Animals, Anticonvulsants, Biomarkers, Brain, Clinical Trials as Topic, Cost-Benefit Analysis, Disease Models, Animal, Disease Progression, Drug Discovery, Drug Evaluation, Preclinical, Drug Resistance, Drugs, Investigational, Electroencephalography, Humans, Precipitating Factors, Surrogate markers, Epileptogenesis, Ictogenesis, Therapeutic intervention, Clinical Sciences, Neurology & Neurosurgery
Abstract: A biomarker is defined as an objectively measured characteristic of a normal or pathologic biologic process. Identification and proper validation of biomarkers of epileptogenesis (the development of epilepsy) and ictogenesis (the propensity to generate spontaneous seizures) might predict the development of an epilepsy condition; identify the presence and severity of tissue capable of generating spontaneous seizures; measure progression after the condition is established; and determine pharmacoresistance. Such biomarkers could be used to create animal models for more cost-effective screening of potential antiepileptogenic and antiseizure drugs and devices, and to reduce the cost of clinical trials by enriching the trial population, and acting as surrogate markers to shorten trial duration. The objectives of the biomarker subgroup for the London Workshop were to define approaches for identifying possible biomarkers for these purposes. Research to identify reliable biomarkers may also reveal underlying mechanisms that could serve as therapeutic targets for the development of new antiepileptogenic and antiseizure compounds.
Published: 2013

9. Finding a better drug for epilepsy: Antiinflammatory targets

Author: Dedeurwaerdere, Stefanie, Friedman, Alon, Fabene, Paolo F, Mazarati, Andrèy, Murashima, Yoshiya L, Vezzani, Annamaria, and Baram, Tallie Z
Subjects: Brain Disorders, Neurodegenerative, Epilepsy, Neurosciences, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Neurological, Anti-Inflammatory Agents, Cell Adhesion Molecules, Humans, Inflammation, Brain inflammation, Epileptogenesis, Therapy, Disease-modifying, Clinical Sciences, Neurology & Neurosurgery
Abstract: This monograph summarizes one of the sessions of the XI Workshop on Neurobiology of Epilepsy (WONOEP), and provides a critical review of the current state of the field. Speakers and discussants focused on several broad topics: (1) the coexistence of inflammatory processes encompassing several distinct signal-transduction pathways with the epileptogenic process; (2) evidence for the contribution of specific inflammatory molecules and processes to the onset and progression of epilepsy, as well as to epilepsy-related morbidities including depression; (3) the complexity and intricate cross-talk of the pathways involved in inflammation, and the discrete, often opposite roles of a given mediator in neurons versus other cell types. These complexities highlight the challenges confronting the field as it aims to define inflammatory molecules as promising targets for epilepsy prevention and treatment.
Published: 2012

10. The role of inflammation in epilepsy

Author: Vezzani, Annamaria, French, Jacqueline, Bartfai, Tamas, and Baram, Tallie Z
Subjects: Biomedical and Clinical Sciences, Neurosciences, Neurodegenerative, Brain Disorders, Epilepsy, Aetiology, 2.1 Biological and endogenous factors, Neurological, Adaptive Immunity, Animals, Encephalitis, Humans, Immunity, Innate, Clinical sciences
Abstract: Epilepsy is the third most common chronic brain disorder, and is characterized by an enduring predisposition to generate seizures. Despite progress in pharmacological and surgical treatments of epilepsy, relatively little is known about the processes leading to the generation of individual seizures, and about the mechanisms whereby a healthy brain is rendered epileptic. These gaps in our knowledge hamper the development of better preventive treatments and cures for the approximately 30% of epilepsy cases that prove resistant to current therapies. Here, we focus on the rapidly growing body of evidence that supports the involvement of inflammatory mediators-released by brain cells and peripheral immune cells-in both the origin of individual seizures and the epileptogenic process. We first describe aspects of brain inflammation and immunity, before exploring the evidence from clinical and experimental studies for a relationship between inflammation and epilepsy. Subsequently, we discuss how seizures cause inflammation, and whether such inflammation, in turn, influences the occurrence and severity of seizures, and seizure-related neuronal death. Further insight into the complex role of inflammation in the generation and exacerbation of epilepsy should yield new molecular targets for the design of antiepileptic drugs, which might not only inhibit the symptoms of this disorder, but also prevent or abrogate disease pathogenesis.
Published: 2011

11. Astrocytes in the initiation and progression of epilepsy

Author: Annamaria Vezzani, Teresa Ravizza, Peter Bedner, Eleonora Aronica, Christian Steinhäuser, and Detlev Boison
Subjects: Neurons, Cellular and Molecular Neuroscience, Epilepsy, Seizures, Astrocytes, Humans, Neurology (clinical)
Abstract: Epilepsy affects ~65 million people worldwide. First-line treatment options include >20 antiseizure medications, but seizure control is not achieved in approximately one-third of patients. Antiseizure medications act primarily on neurons and can provide symptomatic control of seizures, but do not alter the onset and progression of epilepsy and can cause serious adverse effects. Therefore, medications with new cellular and molecular targets and mechanisms of action are needed. Accumulating evidence indicates that astrocytes are crucial to the pathophysiological mechanisms of epilepsy, raising the possibility that these cells could be novel therapeutic targets. In this Review, we discuss how dysregulation of key astrocyte functions — gliotransmission, cell metabolism and immune function — contribute to the development and progression of hyperexcitability in epilepsy. We consider strategies to mitigate astrocyte dysfunction in each of these areas, and provide an overview of how astrocyte activation states can be monitored in vivo not only to assess their contribution to disease but also to identify markers of disease processes and treatment effects. Improved understanding of the roles of astrocytes in epilepsy has the potential to lead to novel therapies to prevent the initiation and progression of epilepsy.
Published: 2022

12. Blood feeding habits of mosquitoes: hardly a bite in South America

Author: Karelly, Melgarejo-Colmenares, María Victoria, Cardo, and Darío, Vezzani
Subjects: Culex, Habits, Infectious Diseases, General Veterinary, Aedes, Insect Science, Animals, Humans, Parasitology, Feeding Behavior, Mosquito Vectors, General Medicine, Brazil
Abstract: Mosquito blood feeding plays a key role in epidemiology. Despite its importance and large number of studies worldwide, less attention has been paid in South America. We summarized some general concepts and methodological issues related to the study of mosquito blood feeding habits, and compiled and analyzed all published information regarding the subject in the continent until 2020. Available literature comprised 152 scientific studies, that pursued different approaches: human landing catches (102 studies), baited trap (19), and blood meal analyses of collected specimens (38). Among the latter, 23 used serological and 15 molecular techniques. Species most frequently studied were those incriminated in malaria transmission, whereas relevant vectors such as Aedes aegypti, Ae. albopictus, and Haemagogus janthinomys were surprisingly neglected. Brazil was the leading country both in number of works and species studied. For over 70% of the species and three out of 13 South American countries there is no single information on mosquito blood feeding habits. Data from baited traps included 143 mosquito species, 83.9% of which were attracted to humans, either exclusively (10.5%) or in combination with other vertebrates (73.4%). Host blood identification of field collected specimens provided data on 102 mosquito species, and 60.8% of these fed on humans (55.9% combined with other vertebrates). Only 17 of the 73 species assessed by both methods yielded similar feeding patterns. Finally, supplementary tables are provided in a comprehensive summary of all information available and information gaps are highlighted for future research in the continent.
Published: 2022

13. GABAA receptor function is enhanced by Interleukin-10 in human epileptogenic gangliogliomas and its effect is counteracted by Interleukin-1β

Author: Gabriele Ruffolo, Veronica Alfano, Alessia Romagnolo, Till Zimmer, James D. Mills, Pierangelo Cifelli, Alessandro Gaeta, Alessandra Morano, Jasper Anink, Angelika Mühlebner, Annamaria Vezzani, Eleonora Aronica, Eleonora Palma, Graduate School, Pathology, APH - Aging & Later Life, APH - Mental Health, and ANS - Cellular & Molecular Mechanisms
Subjects: Adult, Drug Resistant Epilepsy, Multidisciplinary, Immunologic, GABA-A, Receptors, Interleukin-1beta, Humans, Child, Receptors, GABA-A, Interleukin-10, Receptors, Interleukin-10, Receptors, Immunologic, gamma-Aminobutyric Acid, Ganglioglioma
Abstract: Gangliogliomas (GGs) are low-grade brain tumours that cause intractable focal epilepsy in children and adults. In GG, as in epileptogenic focal malformations (i.e., tuberous sclerosis complex, TSC), there is evidence of sustained neuroinflammation with involvement of the pro-inflammatory cytokine IL-1β. On the other hand, anti-inflammatory mediators are less studied but bear relevance for understanding seizure mechanisms. Therefore, we investigated the effect of the key anti-inflammatory cytokine IL-10 on GABAergic neurotransmission in GG. We assessed the IL-10 dependent signaling by transcriptomic analysis, immunohistochemistry and performed voltage-clamp recordings on Xenopus oocytes microtransplanted with cell membranes from brain specimens, to overcome the limited availability of acute GG slices. We report that IL-10-related mRNAs were up-regulated in GG and slightly in TSC. Moreover, we found IL-10 receptors are expressed by neurons and astroglia. Furthermore, GABA currents were potentiated significantly by IL-10 in GG. This effect was time and dose-dependent and inhibited by blockade of IL-10 signaling. Notably, in the same tissue, IL-1β reduced GABA current amplitude and prevented the IL-10 effect. These results suggest that in epileptogenic tissue, pro-inflammatory mechanisms of hyperexcitability prevail over key anti-inflammatory pathways enhancing GABAergic inhibition. Hence, boosting the effects of specific anti-inflammatory molecules could resolve inflammation and reduce intractable seizures.
Published: 2022

14. Safety and Efficacy of Natalizumab as Adjunctive Therapy for People With Drug-Resistant Epilepsy

Author: Jacqueline A, French, Andrew J, Cole, Edward, Faught, William H, Theodore, Annamaria, Vezzani, Kore, Liow, Jonathan J, Halford, Robert, Armstrong, Jerzy P, Szaflarski, Sarah, Hubbard, Jagdish, Patel, Kun, Chen, Wei, Feng, Marco, Rizzo, Jacob, Elkins, Gabrielle, Knafler, Kimberly A, Parkerson, and Jose, Rafecas
Subjects: Adult, Drug Resistant Epilepsy, medicine.medical_specialty, business.industry, Seizure types, Natalizumab, Phases of clinical research, Odds ratio, Placebo, medicine.disease, Epilepsy, Treatment Outcome, Seizures, Internal medicine, Humans, Medicine, Anticonvulsants, Neurology (clinical), business, Adverse effect, medicine.drug
Abstract: Background and ObjectivesTo explore efficacy/safety of natalizumab, a humanized monoclonal anti–α4-integrin antibody, as adjunctive therapy in adults with drug-resistant focal epilepsy.MethodsParticipants with ≥6 seizures during the 6-week baseline period were randomized 1:1 to receive natalizumab 300 mg IV or placebo every 4 weeks for 24 weeks. Primary efficacy outcome was change from baseline in log-transformed seizure frequency, with a predefined threshold for therapeutic success of 31% relative reduction in seizure frequency over the placebo group. Countable seizure types were focal aware with motor signs, focal impaired awareness, and focal to bilateral tonic-clonic. Secondary efficacy endpoints/safety were also assessed.ResultsOf 32 and 34 participants dosed in the natalizumab 300 mg and placebo groups, 30 (94%) and 31 (91%) completed the placebo-controlled treatment period, respectively (one participant was randomized to receive natalizumab but not dosed due to IV complications). Estimated relative change in seizure frequency of natalizumab over placebo was −14.4% (95% confidence interval [CI] –46.1%–36.1%; p = 0.51). The proportion of participants with ≥50% reduction from baseline in seizure frequency was 31.3% for natalizumab and 17.6% for placebo (odds ratio 2.09, 95% CI 0.64–6.85; p = 0.22). Adverse events were reported in 24 (75%) and 22 (65%) participants receiving natalizumab vs placebo.DiscussionAlthough the threshold to demonstrate efficacy was not met, there were no unexpected safety findings and further exploration of possible anti-inflammatory therapies for drug-resistant epilepsy is warranted.Trial Registration InformationThe ClinicalTrials.gov registration number is NCT03283371.Classification of EvidenceThis study provides Class I evidence that IV natalizumab every 4 weeks, compared to placebo, did not significantly change seizure frequency in adults with drug-resistant epilepsy. The study lacked the precision to exclude an important effect of natalizumab.
Published: 2021

15. Cholesterol 24-hydroxylase is a novel pharmacological target for anti-ictogenic and disease modification effects in epilepsy

Author: Alessia Salamone, Gaetano Terrone, Rossella Di Sapia, Silvia Balosso, Teresa Ravizza, Luca Beltrame, Ilaria Craparotta, Laura Mannarino, Sara Raimondi Cominesi, Massimo Rizzi, Alberto Pauletti, Sergio Marchini, Luca Porcu, Till S. Zimmer, Eleonora Aronica, Matthew During, Brett Abrahams, Shinichi Kondo, Toshiya Nishi, Annamaria Vezzani, Salamone, Alessia, Terrone, Gaetano, Di Sapia, Rossella, Balosso, Silvia, Ravizza, Teresa, Beltrame, Luca, Craparotta, Ilaria, Mannarino, Laura, Cominesi, Sara Raimondi, Rizzi, Massimo, Pauletti, Alberto, Marchini, Sergio, Porcu, Luca, Zimmer, Till S., Aronica, Eleonora, During, Matthew, Abrahams, Brett, Kondo, Shinichi, Nishi, Toshiya, Vezzani, Annamaria, Pathology, APH - Aging & Later Life, APH - Mental Health, and ANS - Cellular & Molecular Mechanisms
Subjects: Epilepsy, Pyridines, Status epilepticu, Hippocampus, Epileptogenesis, Neuroprotection, Disease Models, Animal, Mice, Cholesterol, Neurology, Epilepsy, Temporal Lobe, Piperidines, Seizures, Glia, Cholesterol 24-Hydroxylase, Animals, Humans, RNA, Temporal lobe epilepsy, Status epilepticus
Abstract: Therapies for epilepsy mainly provide symptomatic control of seizures since most of the available drugs do not target disease mechanisms. Moreover, about one-third of patients fail to achieve seizure control. To address the clinical need for disease-modifying therapies, research should focus on targets which permit interventions finely balanced between optimal efficacy and safety. One potential candidate is the brain-specific enzyme cholesterol 24-hydroxylase. This enzyme converts cholesterol to 24S-hydroxycholesterol, a metabolite which among its biological roles modulates neuronal functions relevant for hyperexcitability underlying seizures. To study the role of cholesterol 24-hydroxylase in epileptogenesis, we administered soticlestat (TAK-935/OV935), a potent and selective brain-penetrant inhibitor of the enzyme, during the early disease phase in a mouse model of acquired epilepsy using a clinically relevant dose. During soticlestat treatment, the onset of epilepsy was delayed and the number of ensuing seizures was decreased by about 3-fold compared to vehicle-treated mice, as assessed by EEG monitoring. Notably, the therapeutic effect was maintained 6.5 weeks after drug wash-out when seizure number was reduced by about 4-fold and their duration by 2-fold. Soticlestat-treated mice showed neuroprotection of hippocampal CA1 neurons and hilar mossy cells as assessed by post-mortem brain histology. High throughput RNA-sequencing of hippocampal neurons and glia in mice treated with soticlestat during epileptogenesis showed that inhibition of cholesterol 24-hydroxylase did not directly affect the epileptogenic transcriptional network, but rather modulated a non-overlapping set of genes that might oppose the pathogenic mechanisms of the disease. In human temporal lobe epileptic foci, we determined that cholesterol 24-hydroxylase expression trends higher in neurons, similarly to epileptic mice, while the enzyme is ectopically induced in astrocytes compared to control specimens. Soticlestat reduced significantly the number of spontaneous seizures in chronic epileptic mice when was administered during established epilepsy. Data show that cholesterol 24-hydroxylase contributes to spontaneous seizures and is involved in disease progression, thus it represents a novel target for chronic seizures inhibition and disease-modification therapy in epilepsy.
Published: 2022

16. Clinical factors associated with death in 3044 COVID-19 patients managed in internal medicine wards in Italy: comment

Author: Bandera, A., Nobili, A., Tettamanti, M., Harari, S., Bosari, S., Mannucci, P. M., Scudeller, L., Fusetti, G., Rusconi, L., Dell'Orto, S., Prati, D., Valenti, L., Giovannelli, S., Manunta, M., Lamorte, G., Ferrari, F., Gori, A., Muscatello, A., Mangioni, D., Alagna, L., Bozzi, G., Lombardi, A., Ungaro, R., Ancona, G., Zuglian, G., Bolis, M., Iannotti, N., Ludovisi, S., Comelli, A., Renisi, G., Biscarini, S., Castelli, V., Palomba, E., Fava, M., Fortina, V., Peri, C. A., Saltini, P., Viero, G., Itri, T., Ferroni, V., Pastore, V., Massafra, R., Liparoti, A., Muheberimana, T., Giommi, A., Bianco, R., De Azevedo, R. M., Chitani, G. E., Peyvandi, F., Gualtierotti, R., Ferrari, B., Rossio, R., Boasi, N., Pagliaro, E., Massimo, C., De Caro, M., Montano, N., Vigone, B., Bellocchi, C., Carandina, A., Fiorelli, E., Melli, V., Tobaldini, E., Blasi, F., Aliberti, S., Spotti, M., Terranova, L., Misuraca, S., D'Adda, A., Della Fiore, S., Di Pasquale, M., Contarini, M. M. M., Ori, M., Morlacchi, L., Rossetti, V., Gramegna, A., Pappalettera, M., Cavallini, M., Buscemi, A., Vicenzi, M., Rota, I., Costantino, G., Solbiati, M., Furlan, L., Mancarella, M., Colombo, G., Fanin, A., Passarella, M., Monzani, V., Canetta, C., Rovellini, A., Barbetta, L., Billi, F., Folli, C., Accordino, S., Maira, D., C. M., Hu, Motta, I., Scaramellini, N., Fracanzani, A. L., Lombardi, R., Cespiati, A., Cesari, M., Lucchi, T., Proietti, M., Calcaterra, L., Mandelli, C., Coppola, C., Cerizza, A., Pesenti, A. M., Grasselli, G., Galazzi, A., Monti, I., Galbussera, A. A., Crisafulli, E., Girelli, D., Maroccia, A., Gabbiani, D., Busti, F., Vianello, A., Biondan, M., Sartori, F., Faverio, P., Pesci, A., Zucchetti, S., Bonfanti, P., Rossi, M., Beretta, I., Spolti, A., Elia, D., Cassandro, R., Caminati, A., Cipollone, F., Guagnano, M. T., D'Ardes, D., Rossi, I., Vezzani, F., Spanevello, A., Cherubino, F., Visca, D., Contoli, M., Papi, A., Morandi, L., Battistini, N., Moreo, G. L., Iannuzzi, P., Fumagalli, D., Leone, S., Bandera, A, Nobili, A, Tettamanti, M, Harari, S, Bosari, S, Mannucci, P, Scudeller, L, Fusetti, G, Rusconi, L, Dell'Orto, S, Prati, D, Valenti, L, Giovannelli, S, Manunta, M, Lamorte, G, Ferrari, F, Gori, A, Muscatello, A, Mangioni, D, Alagna, L, Bozzi, G, Lombardi, A, Ungaro, R, Ancona, G, Zuglian, G, Bolis, M, Iannotti, N, Ludovisi, S, Comelli, A, Renisi, G, Biscarini, S, Castelli, V, Palomba, E, Fava, M, Fortina, V, Peri, C, Saltini, P, Viero, G, Itri, T, Ferroni, V, Pastore, V, Massafra, R, Liparoti, A, Muheberimana, T, Giommi, A, Bianco, R, De Azevedo, R, Chitani, G, Peyvandi, F, Gualtierotti, R, Ferrari, B, Rossio, R, Boasi, N, Pagliaro, E, Massimo, C, De Caro, M, Montano, N, Vigone, B, Bellocchi, C, Carandina, A, Fiorelli, E, Melli, V, Tobaldini, E, Blasi, F, Aliberti, S, Spotti, M, Terranova, L, Misuraca, S, D'Adda, A, Della Fiore, S, Di Pasquale, M, Contarini, M, Ori, M, Morlacchi, L, Rossetti, V, Gramegna, A, Pappalettera, M, Cavallini, M, Buscemi, A, Vicenzi, M, Rota, I, Costantino, G, Solbiati, M, Furlan, L, Mancarella, M, Colombo, G, Fanin, A, Passarella, M, Monzani, V, Canetta, C, Rovellini, A, Barbetta, L, Billi, F, Folli, C, Accordino, S, Maira, D, Hu, C, Motta, I, Scaramellini, N, Fracanzani, A, Lombardi, R, Cespiati, A, Cesari, M, Lucchi, T, Proietti, M, Calcaterra, L, Mandelli, C, Coppola, C, Cerizza, A, Pesenti, A, Grasselli, G, Galazzi, A, Monti, I, Galbussera, A, Crisafulli, E, Girelli, D, Maroccia, A, Gabbiani, D, Busti, F, Vianello, A, Biondan, M, Sartori, F, Faverio, P, Pesci, A, Zucchetti, S, Bonfanti, P, Rossi, M, Beretta, I, Spolti, A, Elia, D, Cassandro, R, Caminati, A, Cipollone, F, Guagnano, M, D'Ardes, D, Rossi, I, Vezzani, F, Spanevello, A, Cherubino, F, Visca, D, Contoli, M, Papi, A, Morandi, L, Battistini, N, Moreo, G, Iannuzzi, P, Fumagalli, D, and Leone, S
Subjects: Adult, medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Critical Care, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Ce - Letter to the Editor, MEDLINE, Cohort Studies, Hospital, Internal Medicine, Medicine, Humans, Hospital Mortality, Intensive care medicine, Aged, Aged, 80 and over, business.industry, SARS-CoV-2, COVID-19, Middle Aged, Respiration, Artificial, Hospitals, Hospitalization, Survival Rate, Italy, Emergency Medicine, business, Human
Abstract: During the COVID-19 2020 outbreak, a large body of data has been provided on general management and outcomes of hospitalized COVID-19 patients. Yet, relatively little is known on characteristics and outcome of patients managed in Internal Medicine Units (IMU). To address this gap, the Italian Society of Internal Medicine has conducted a nationwide cohort multicentre study on death outcome in adult COVID-19 patients admitted and managed in IMU. This study assessed 3044 COVID-19 patients at 41 referral hospitals across Italy from February 3rd to May 8th 2020. Demographics, comorbidities, organ dysfunction, treatment, and outcomes including death were assessed. During the study period, 697 patients (22.9%) were transferred to intensive care units, and 351 died in IMU (death rate 14.9%). At admission, factors independently associated with in-hospital mortality were age (OR 2.46, p = 0.000), productive cough (OR 2.04, p = 0.000), pre-existing chronic heart failure (OR 1.58, p = 0.017) and chronic obstructive pulmonary disease (OR 1.17, p = 0.048), the number of comorbidities (OR 1.34, p = 0.000) and polypharmacy (OR 1.20, p = 0.000). Of note, up to 40% of elderly patients did not report fever at admission. Decreasing PaO
Published: 2022

17. GABA

Author: Gabriele, Ruffolo, Veronica, Alfano, Alessia, Romagnolo, Till, Zimmer, James D, Mills, Pierangelo, Cifelli, Alessandro, Gaeta, Alessandra, Morano, Jasper, Anink, Angelika, Mühlebner, Annamaria, Vezzani, Eleonora, Aronica, and Eleonora, Palma
Subjects: Adult, Drug Resistant Epilepsy, Interleukin-1beta, Humans, Receptors, Interleukin-10, Receptors, Immunologic, Child, Receptors, GABA-A, gamma-Aminobutyric Acid, Ganglioglioma, Interleukin-10
Abstract: Gangliogliomas (GGs) are low-grade brain tumours that cause intractable focal epilepsy in children and adults. In GG, as in epileptogenic focal malformations (i.e., tuberous sclerosis complex, TSC), there is evidence of sustained neuroinflammation with involvement of the pro-inflammatory cytokine IL-1β. On the other hand, anti-inflammatory mediators are less studied but bear relevance for understanding seizure mechanisms. Therefore, we investigated the effect of the key anti-inflammatory cytokine IL-10 on GABAergic neurotransmission in GG. We assessed the IL-10 dependent signaling by transcriptomic analysis, immunohistochemistry and performed voltage-clamp recordings on Xenopus oocytes microtransplanted with cell membranes from brain specimens, to overcome the limited availability of acute GG slices. We report that IL-10-related mRNAs were up-regulated in GG and slightly in TSC. Moreover, we found IL-10 receptors are expressed by neurons and astroglia. Furthermore, GABA currents were potentiated significantly by IL-10 in GG. This effect was time and dose-dependent and inhibited by blockade of IL-10 signaling. Notably, in the same tissue, IL-1β reduced GABA current amplitude and prevented the IL-10 effect. These results suggest that in epileptogenic tissue, pro-inflammatory mechanisms of hyperexcitability prevail over key anti-inflammatory pathways enhancing GABAergic inhibition. Hence, boosting the effects of specific anti-inflammatory molecules could resolve inflammation and reduce intractable seizures.
Published: 2022

18. [Surveillance of the dengue vector at its distribution limit. A collaborative experience between the scientific, municipal and citizen ambits]

Author: Darío, Vezzani, Hernán, Cetraro, and Federico, Sánchez Chopa
Subjects: Dengue, Aedes, Argentina, Animals, Humans, Mosquito Vectors, Cities
Abstract: In Argentina, during the last decade a southward expansion of the mosquito Aedes aegypti has been observed, accompanied by an expansion in the dengue transmission. The objective of this study was to assess the establishment of the dengue mosquito vector in a locality next to its distribution limits by a collaborative work among scientific, municipal and citizen ambits.A vector surveillance system through ovitraps was implemented, and it was complemented by pictures and mosquitoes captured by citizens, and by the active search of breeding sites in different urban spaces of Tandil City, Argentina.The establishment of Aedes aegypti population in the city was demonstrated, both by ovitraps and citizen science contributions. This information made it possible to begin to make the problem visible among municipal authorities and citizens.Dengue is an invisible disease in localities in which the mosquito vector has been spreading during the last decade. The information produced by the entomological surveillance is the necessary basis to addresssocial communication to produce behavioral changes in the responsible authorities as well as in the families.Introducción: En Argentina, durante la última década se ha observado una expansión hacia el sur del mosquito Aedes aegypti, acompañada por la expansión en la transmisión del dengue. El objetivo de este estudio fue evaluar el establecimiento de Ae. aegypti en una localidad cercana al límite de su distribución mediante un trabajo colaborativo entre los ámbitos científico, municipal, y ciudadano. Métodos: Se implementó un sistema de vigilancia del vector mediante ovitrampas, el cual se complementó con fotografías y ejemplares aportados por los ciudadanos, y con búsqueda activa de criaderos del mosquito en distintos espacios urbanos de la ciudad de Tandil, Argentina. Resultados: Se demostró el establecimiento de una población de Ae. aegypti en el municipio, tanto por medio de las ovitrampas como por los aportes del conocimiento y participación de la comunidad: la ciencia ciudadana. La información obtenida permitió comenzar a visibilizar la problemática entre los funcionarios municipales y la ciudadanía. Discusión: El dengue es una enfermedad aún invisible en localidades donde se ha estado expandiendo el mosquito vector durante la última década. La participación pública y la información producida con la vigilancia entomológica es la base necesaria para abordar la comunicación social a fin de producir cambios de conducta en las autoridades responsables y en las familias.
Published: 2022

19. Antiepileptogenesis and disease modification: Progress, challenges, and the path forward—Report of the Preclinical Working Group of the 2018 NINDS‐sponsored antiepileptogenesis and disease modification workshop

Author: Annamaria Vezzani, Kevin J. Staley, Aristea S. Galanopoulou, Terence J. O'Brien, Harald Sontheimer, Brian D. Klein, H. Steve White, John A. Wolf, Wolfgang Löscher, Twyman Roy E, Karen S. Wilcox, Raimondo D'Ambrosio, Laura Lubbers, and Vicky Whittemore
Subjects: medicine.medical_specialty, translation, Disease, Comorbidity, Epilepsy types, Translational Research, Biomedical, Epilepsy, acquired epilepsy, medicine, Humans, National Institute of Neurological Disorders and Stroke (U.S.), RC346-429, Special Report, Medical education, treatment, business.industry, Public health, Clinical study design, animal model, medicine.disease, United States, Clinical trial, Data sharing, Stroke, Neurology, Disease modification, Special Reports, Neurology. Diseases of the nervous system, Neurology (clinical), genetic epilepsy, business
Abstract: Epilepsy is one of the most common chronic brain diseases and is often associated with cognitive, behavioral, or other medical conditions. The need for therapies that would prevent, ameliorate, or cure epilepsy and the attendant comorbidities is a priority for both epilepsy research and public health. In 2018, the National Institute of Neurological Disease and Stroke (NINDS) convened a workshop titled “Accelerating the Development of Therapies for Antiepileptogenesis and Disease Modification” that brought together preclinical and clinical investigators and industry and regulatory bodies’ representatives to discuss and propose a roadmap to accelerate the development of antiepileptogenic (AEG) and disease‐modifying (DM) new therapies. This report provides a summary of the discussions and proposals of the Preclinical Science working group. Highlights of the progress of collaborative preclinical research projects on AEG/DM of ongoing research initiatives aiming to improve infrastructure and translation to clinical trials are presented. Opportunities and challenges of preclinical epilepsy research, vis‐à‐vis clinical research, were extensively discussed, as they pertain to modeling of specific epilepsy types across etiologies and ages, the utilization of preclinical models in AG/DM studies, and the strategies and study designs, as well as on matters pertaining to transparency, data sharing, and reporting research findings. A set of suggestions on research initiatives, infrastructure, workshops, advocacy, and opportunities for expanding the borders of epilepsy research were discussed and proposed as useful initiatives that could help create a roadmap to accelerate and optimize preclinical translational AEG/DM epilepsy research.
Published: 2021

20. Proposal to optimize evaluation and treatment of Febrile infection‐related epilepsy syndrome (FIRES): A Report from FIRES workshop

Author: Elaine C. Wirrell, Jessica L. Carpenter, Eyal Muscal, Andreas Brunklaus, Elizabeth Wells, Rima Nabbout, Ronny Wickström, James J. Riviello, William P Roche, Krista Eschbach, Annamaria Vezzani, Mark Gorman, Coral M. Stredny, Marios Kaliakatsos, Antonio Valentin, Eric T. Payne, Tara K. Mangum, Sookyong Koh, Craig A. Press, Yi-Chen Lai, and Kihyeong Lee
Subjects: Drug Resistant Epilepsy, Pediatrics, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Status epilepticus, lcsh:RC346-429, Seizures, Febrile, immune activation, neuroinflammation, Epilepsy, Status Epilepticus, Cannabidiol, Humans, Medicine, new‐onset refractory status epilepticus, Young adult, Child, Special Report, lcsh:Neurology. Diseases of the nervous system, Anakinra, business.industry, Epileptic encephalopathy, Infant, medicine.disease, cytokines, Interleukin 1 Receptor Antagonist Protein, Febrile infection related epilepsy syndrome, epileptic encephalopathy, Immune System Diseases, Special Reports, Neurology, Child, Preschool, Epilepsy syndromes, Encephalitis, Neurology (clinical), medicine.symptom, Diet, Ketogenic, business, Epileptic Syndromes, anakinra, medicine.drug, Ketogenic diet
Abstract: Febrile infection‐related epilepsy syndrome (FIRES) is a rare catastrophic epileptic encephalopathy that presents suddenly in otherwise normal children and young adults causing significant neurological disability, chronic epilepsy, and high rates of mortality. To suggest a therapy protocol to improve outcome of FIRES, workshops were held in conjunction with American Epilepsy Society annual meeting between 2017 and 2019. An international group of pediatric epileptologists, pediatric neurointensivists, rheumatologists and basic scientists with interest and expertise in FIRES convened to propose an algorithm for a standardized approach to the diagnosis and treatment of FIRES. The broad differential for refractory status epilepticus (RSE) should include FIRES, to allow empiric therapies to be started early in the clinical course. FIRES should be considered in all previously healthy patients older than two years of age who present with explosive onset of seizures rapidly progressing to RSE, following a febrile illness in the preceding two weeks. Once FIRES is suspected, early administrations of ketogenic diet and anakinra (the IL‐1 receptor antagonist that blocks biologic activity of IL‐1β) are recommended.
Published: 2021

21. Common cardiovascular risk factors and in-hospital mortality in 3,894 patients with COVID-19: survival analysis and machine learning-based findings from the multicentre Italian CORIST Study

Author: Augusto Di Castelnuovo, Marialaura Bonaccio, Simona Costanzo, Alessandro Gialluisi, Andrea Antinori, Nausicaa Berselli, Lorenzo Blandi, Raffaele Bruno, Roberto Cauda, Giovanni Guaraldi, Ilaria My, Lorenzo Menicanti, Giustino Parruti, Giuseppe Patti, Stefano Perlini, Francesca Santilli, Carlo Signorelli, Giulio G. Stefanini, Alessandra Vergori, Amina Abdeddaim, Walter Ageno, Antonella Agodi, Piergiuseppe Agostoni, Luca Aiello, Samir Al Moghazi, Filippo Aucella, Greta Barbieri, Alessandro Bartoloni, Carolina Bologna, Paolo Bonfanti, Serena Brancati, Francesco Cacciatore, Lucia Caiano, Francesco Cannata, Laura Carrozzi, Antonio Cascio, Antonella Cingolani, Francesco Cipollone, Claudia Colomba, Annalisa Crisetti, Francesca Crosta, Gian B. Danzi, Damiano D'Ardes, Katleen de Gaetano Donati, Francesco Di Gennaro, Gisella Di Palma, Giuseppe Di Tano, Massimo Fantoni, Tommaso Filippini, Paola Fioretto, Francesco M. Fusco, Ivan Gentile, Leonardo Grisafi, Gabriella Guarnieri, Francesco Landi, Giovanni Larizza, Armando Leone, Gloria Maccagni, Sandro Maccarella, Massimo Mapelli, Riccardo Maragna, Rossella Marcucci, Giulio Maresca, Claudia Marotta, Lorenzo Marra, Franco Mastroianni, Alessandro Mengozzi, Francesco Menichetti, Jovana Milic, Rita Murri, Arturo Montineri, Roberta Mussinelli, Cristina Mussini, Maria Musso, Anna Odone, Marco Olivieri, Emanuela Pasi, Francesco Petri, Biagio Pinchera, Carlo A. Pivato, Roberto Pizzi, Venerino Poletti, Francesca Raffaelli, Claudia Ravaglia, Giulia Righetti, Andrea Rognoni, Marco Rossato, Marianna Rossi, Anna Sabena, Francesco Salinaro, Vincenzo Sangiovanni, Carlo Sanrocco, Antonio Scarafino, Laura Scorzolini, Raffaella Sgariglia, Paola G. Simeone, Enrico Spinoni, Carlo Torti, Enrico M. Trecarichi, Francesca Vezzani, Giovanni Veronesi, Roberto Vettor, Andrea Vianello, Marco Vinceti, Raffaele De Caterina, Licia Iacoviello, Di Castelnuovo, A., Bonaccio, M., Costanzo, S., Gialluisi, A., Antinori, A., Berselli, N., Blandi, L., Bruno, R., Cauda, R., Guaraldi, G., My, I., Menicanti, L., Parruti, G., Patti, G., Perlini, S., Santilli, F., Signorelli, C., Stefanini, G. G., Vergori, A., Abdeddaim, A., Ageno, W., Agodi, A., Agostoni, P., Aiello, L., Al Moghazi, S., Aucella, F., Barbieri, G., Bartoloni, A., Bologna, C., Bonfanti, P., Brancati, S., Cacciatore, F., Caiano, L., Cannata, F., Carrozzi, L., Cascio, A., Cingolani, A., Cipollone, F., Colomba, C., Crisetti, A., Crosta, F., Danzi, G. B., D'Ardes, D., de Gaetano Donati, K., Di Gennaro, F., Di Palma, G., Di Tano, G., Fantoni, M., Filippini, T., Fioretto, P., Fusco, F. M., Gentile, I., Grisafi, L., Guarnieri, G., Landi, F., Larizza, G., Leone, A., Maccagni, G., Maccarella, S., Mapelli, M., Maragna, R., Marcucci, R., Maresca, G., Marotta, C., Marra, L., Mastroianni, F., Mengozzi, A., Menichetti, F., Milic, J., Murri, R., Montineri, A., Mussinelli, R., Mussini, C., Musso, M., Odone, A., Olivieri, M., Pasi, E., Petri, F., Pinchera, B., Pivato, C. A., Pizzi, R., Poletti, V., Raffaelli, F., Ravaglia, C., Righetti, G., Rognoni, A., Rossato, M., Rossi, M., Sabena, A., Salinaro, F., Sangiovanni, V., Sanrocco, C., Scarafino, A., Scorzolini, L., Sgariglia, R., Simeone, P. G., Spinoni, E., Torti, C., Trecarichi, E. M., Vezzani, F., Veronesi, G., Vettor, R., Vianello, A., Vinceti, M., De Caterina, R., Iacoviello, L., Di Castelnuovo, Augusto, Bonaccio, Marialaura, Costanzo, Simona, Gialluisi, Alessandro, Antinori, Andrea, Berselli, Nausicaa, Blandi, Lorenzo, Bruno, Raffaele, Cauda, Roberto, Guaraldi, Giovanni, My, Ilaria, Menicanti, Lorenzo, Parruti, Giustino, Patti, Giuseppe, Perlini, Stefano, Santilli, Francesca, Signorelli, Carlo, Stefanini, Giulio G, Vergori, Alessandra, Abdeddaim, Amina, Ageno, Walter, Agodi, Antonella, Agostoni, Piergiuseppe, Aiello, Luca, Al Moghazi, Samir, Aucella, Filippo, Barbieri, Greta, Bartoloni, Alessandro, Bologna, Carolina, Bonfanti, Paolo, Brancati, Serena, Cacciatore, Francesco, Caiano, Lucia, Cannata, Francesco, Carrozzi, Laura, Cascio, Antonio, Cingolani, Antonella, Cipollone, Francesco, Colomba, Claudia, Crisetti, Annalisa, Crosta, Francesca, Danzi, Gian B, D'Ardes, Damiano, de Gaetano Donati, Katleen, Di Gennaro, Francesco, Di Palma, Gisella, Di Tano, Giuseppe, Fantoni, Massimo, Filippini, Tommaso, Fioretto, Paola, Fusco, Francesco M, Gentile, Ivan, Grisafi, Leonardo, Guarnieri, Gabriella, Landi, Francesco, Larizza, Giovanni, Leone, Armando, Maccagni, Gloria, Maccarella, Sandro, Mapelli, Massimo, Maragna, Riccardo, Marcucci, Rossella, Maresca, Giulio, Marotta, Claudia, Marra, Lorenzo, Mastroianni, Franco, Mengozzi, Alessandro, Menichetti, Francesco, Milic, Jovana, Murri, Rita, Montineri, Arturo, Mussinelli, Roberta, Mussini, Cristina, Musso, Maria, Odone, Anna, Olivieri, Marco, Pasi, Emanuela, Petri, Francesco, Pinchera, Biagio, Pivato, Carlo A, Pizzi, Roberto, Poletti, Venerino, Raffaelli, Francesca, Ravaglia, Claudia, Righetti, Giulia, Rognoni, Andrea, Rossato, Marco, Rossi, Marianna, Sabena, Anna, Salinaro, Francesco, Sangiovanni, Vincenzo, Sanrocco, Carlo, Scarafino, Antonio, Scorzolini, Laura, Sgariglia, Raffaella, Simeone, Paola G, Spinoni, Enrico, Torti, Carlo, Trecarichi, Enrico M, Vezzani, Francesca, Veronesi, Giovanni, Vettor, Roberto, Vianello, Andrea, Vinceti, Marco, De Caterina, Raffaele, Iacoviello, Licia, Di Castelnuovo, A, Bonaccio, M, Costanzo, S, Gialluisi, A, Antinori, A, Berselli, N, Blandi, L, Bruno, R, Cauda, R, Guaraldi, G, My, I, Menicanti, L, Parruti, A, Patti, G, Perlini, S, Santilli, F, Signorelli, C, Stefanini, G, Vergori, A, Abdeddaim, A, Ageno, W, Agodi, A, Agostoni, P, Aiello, L, Al Moghazi, S, Aucella, F, Barbieri, G, Bartoloni, A, Bologna, C, Bonfanti, P, Brancati, S, Cacciatore, F, Caiano, L, Cannata, F, Carrozzi, L, Cascio, A, Cingolani, A, Cipollone, F, Colomba, C, Crisetti, A, Crosta, F, Danzi, G, D'Ardes, D, de Gaetano Donati, K, Di Gennaro, F, Di Palma, G, Di Tano, G, Fantoni, M, Filippini, T, Fioretto, P, Fusco, F, Gentile, I, Grisafi, L, Guarnieri, G, Landi, F, Larizza, G, Leone, A, Maccagni, G, Maccarella, S, Mapelli, M, Maragna, R, Marcucci, R, Maresca, G, Marotta, C, Marra, L, Mastroianni, F, Mengozzi, A, Menichetti, F, Milic, J, Miurri, R, Montineri, A, Mussinelli, R, Mussini, C, Musso, M, Odone, A, Olivieri, M, Pasi, E, Petri, F, Pinchera, B, Pivato, C, Pizzi, R, Poletti, V, Raffaelli, F, Ravaglia, C, Righetti, G, Rognoni, A, Rossato, M, Rossi, M, Sabena, A, Salinaro, F, Sangiovanni, V, Sanrocco, C, Scarafino, A, Scorzolini, L, Sgariglia, R, Simeone, P, Spinoni, E, Torti, C, Trecarichi, E, Vezzani, F, Veronesi, G, Vettor, R, Vianello, A, Vinceti, M, De Caterina, R, and Iacoviello, L
Subjects: Male, Epidemiology, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), 030204 cardiovascular system & hematology, computer.software_genre, Machine Learning, 0302 clinical medicine, Retrospective Studie, Risk Factors, Cardiovascular Disease, 80 and over, Medicine, Age Factor, Viral, Hospital Mortality, Betacoronavirus Hospital Mortality, Young adult, Aged, 80 and over, Nutrition and Dietetics, COVID-19, In-hospital mortality, Risk factors, Mortality rate, Hazard ratio, Age Factors, Middle Aged, C-Reactive Protein, Cardiovascular Diseases, Female, Survival Analysi, Cardiology and Cardiovascular Medicine, Coronavirus Infections, Human, Glomerular Filtration Rate, Adult, medicine.medical_specialty, Adolescent, Pneumonia, Viral, 030209 endocrinology & metabolism, Settore MED/17 - MALATTIE INFETTIVE, Machine learning, Aged, Humans, Pandemics, Retrospective Studies, SARS-CoV-2, Survival Analysis, Young Adult, Betacoronavirus, Article, 03 medical and health sciences, Risk factor, Survival analysis, Pandemic, Betacoronaviru, business.industry, Coronavirus Infection, Risk Factor, Retrospective cohort study, Pneumonia, Confidence interval, Artificial intelligence, business, computer
Abstract: Background and aims There is poor knowledge on characteristics, comorbidities and laboratory measures associated with risk for adverse outcomes and in-hospital mortality in European Countries. We aimed at identifying baseline characteristics predisposing COVID-19 patients to in-hospital death. Methods and results Retrospective observational study on 3894 patients with SARS-CoV-2 infection hospitalized from February 19th to May 23rd, 2020 and recruited in 30 clinical centres distributed throughout Italy. Machine learning (random forest)-based and Cox survival analysis. 61.7% of participants were men (median age 67 years), followed up for a median of 13 days. In-hospital mortality exhibited a geographical gradient, Northern Italian regions featuring more than twofold higher death rates as compared to Central/Southern areas (15.6% vs 6.4%, respectively). Machine learning analysis revealed that the most important features in death classification were impaired renal function, elevated C reactive protein and advanced age. These findings were confirmed by multivariable Cox survival analysis (hazard ratio (HR): 8.2; 95% confidence interval (CI) 4.6–14.7 for age ≥85 vs 18–44 y); HR = 4.7; 2.9–7.7 for estimated glomerular filtration rate levels, Highlights • Impaired renal function, elevated C-reactive protein and advanced age were major indicators of death in COVID-19 patients. • These associations were substantially homogenous across all sub-groups analysed. • No relation was found with obesity, tobacco use, cardiovascular disease and related-comorbidities. • Death rates were higher in the Northern as opposed to Central-Southern Italian regions.
Published: 2020

22. Correlation between work impairment, scores of rhinitis severity and asthma using the MASK-air ® App

Author: Bédard, Annabelle, Antó, Josep, Fonseca, Joao, Arnavielhe, Sylvie, Bachert, Claus, Bedbrook, Anna, Bindslev-Jensen, Carsten, Bosnic-Anticevich, Sinthia, Cardona, Victoria, Cruz, Alvaro, Fokkens, Wytske, Garcia-Aymerich, Judith, Hellings, Peter, Ivancevich, Juan, Klimek, Ludger, Kuna, Piotr, Kvedariene, Violeta, Larenas-Linnemann, Désirée, Melen, Erik, Monti, Ricardo, Mösges, Ralf, Mullol, Joaquim, Papadopoulos, Nikos, Pham-Thi, Nhan, Samolinski, Boleslaw, V Tomazic, Peter, Toppila-Salmi, Sanna, Ventura, Maria Teresa, Yorgancioglu, Arzu, Bousquet, Jean, Pfaar, Oliver, Basagana, Xavier, Bosnic‐Anticevich, Sinthia, Pham‐Thi, Nhân, Hellings, PW, Aberer, W., Agache, I., Akdis, Ca, Akdis, M., Aliberti, MR, Almeida, R., Amat, F., Angles, R, Annesi‐Maesano, I, Ansotegui, IJ, Anto, JM, Arnavielle, S, Asayag, E, Asarnoj, A, Arshad, H, Avolio, F, Bacci, E, Baiardini, I, Barbara, C, Barbagallo, M., Baroni, I, Barreto, BA, Basagaña, X., Bateman, ED, Bedolla‐Barajas, M, Bewick, M., Beghé, B., Bel, EH, Bergmann, KC, Bennoor, KS, Benson, M, Bertorello, L, Białoszewski, AZ, Bieber, T., Bialek, S, Bindslev‐Jensen, Carsten, Bjermer, L., Blain, H., Blasi, F., Blua, A, Bochenska Marciniak, M, Bogus‐Buczynska, I, Boner, AL, Bonini, M., Bonini, S., Bosnic‐Anticevich, CS, Bosse, I., Bouchard, J., Boulet, LP, Bourret, R., Bousquet, Pj, Braido, F, Briedis, V, Brightling, CE, Brozek, J, Bucca, C, Buhl, R, Buonaiuto, R, Panaitescu, C, Burguete Cabañas, MT, Burte, E., Bush, A, Caballero‐Fonseca, F, Caillaud, D., Caimmi, D., Calderon, MA, Camargos, PAM, Camuzat, T., Canfora, G, Canonica, Gw, Carlsen, KH, Carreiro‐Martins, P, Carriazo, AM, Carr, W, Cartier, C., Casale, T., Castellano, G, Cecchi, L, Cepeda, AM, Chavannes, NH, Chen, Y., Chiron, R., Chivato, T, Chkhartishvili, E, Chuchalin, AG, Chung, KF, Ciaravolo, MM, Ciceran, A, Cingi, C, Ciprandi, G, Carvalho Coehlo, AC, Colas, L, Colgan, E, Coll, J, Conforti, D, Constantinidis, J, de Sousa, J Correia, Cortés‐Grimaldo, RM, Corti, F, 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J, Hernández, L, Hourihane, JO’B, Huerta‐Villalobos, YR, Humbert, M., Iaccarino, G., Illario, M, Ispayeva, Z, Ivancevich, JC, Jares, EJ, Jassem, E, Johnston, Sl, Joos, G, Jung, KS, Just, J., Jutel, M, Kaidashev, I, Kalayci, O, Kalyoncu, AF, Karjalainen, J, Kardas, P, Keil, T, Keith, PK, Khaitov, M, Khaltaev, N, Kleine‐Tebbe, J, Kowalski, Ml, Kuitunen, M, Kull, I., Kupczyk, M, Krzych‐Fałta, E, Lacwik, P, Larenas‐Linnemann, Désirée, Laune, D., Lauri, D, Lavrut, J, Le, LTT, Lessa, M, Levato, G, Li, J., Lieberman, P, Lipiec, A, Lipworth, B, Lodrup Carlsen, KC, Louis, R, Lourenço, O, Luna‐Pech, JA, Magnan, A., Mahboub, B, Maier, D., Mair, A, Majer, I, Malva, J, Mandajieva, E, Manning, P, De Manuel Keenoy, E, Marshall, GD, Masjedi, MR, Maspero, JF, Mathieu‐Dupas, E, Matta Campos, JJ, Matos, AL, Maurer, M, Mavale‐Manuel, S, Mayora, O, Meco, C, Medina‐Avalos, MA, Melo‐Gomes, E, Meltzer, EO, Menditto, E., Miculinic, N, Mihaltan, F., Milenkovic, B, Moda, G, Mogica‐Martinez, MD, Mohammad, Y, Momas, I., Montefort, S, Mora Bogado, D, Morais‐Almeida, M, Morato‐Castro, FF, Mota‐Pinto, A, Moura Santo, P, Münter, L, Muraro, A, Murray, R, Naclerio, R., Nadif, R., Nalin, M, Napoli, L, Namazova‐Baranova, L, Neffen, H, Niedeberger, V, Nekam, K, Neou, A, Nieto, A, Nogueira‐Silva, L, Nogues, M., Novellino, E, Nyembue, TD, O’Hehir, RE, Odzhakova, C, Ohta, K., Okamoto, Y., Okubo, K, Onorato, GL, Ortega Cisneros, M, Ouédraogo, S., Pali‐Schöll, I, Palkonen, S, Panzner, P, Papadopoulos, NG, Park, HS, Papi, A., Passalacqua, G, Paulino, E, Pawankar, R, Pedersen, S, Pépin, JL, Pereira, AM, Persico, M, PHILLIPS, J, Picard, R., Pigearias, B, Pin, I., Pitsios, C., Plavec, D, Pohl, W, Popov, TA, Portejoie, F., Potter, P, Pozzi, AC, Price, D, Prokopakis, EP, Puy, R, Pugin, B, Pulido Ross, RE, Przemecka, M, Rabe, KF, Raciborski, F, Rajabian‐Soderlund, R, Reitsma, S, Ribeirinho, I, Rimmer, J, Rivero‐Yeverino, D, Rizzo, JA, Rizzo, MC, Robalo‐Cordeiro, C, Rodenas, F, Rodo, X, Rodriguez Gonzalez, M, 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S, Wallace, D, Wang, DY, Waserman, S., Werfel, T, Westman, M, Wickman, M., Williams, DM, Williams, S, Wilson, N, Wright, J, Wroczynski, P, Yakovliev, P, Yawn, BP, Yiallouros, PK, Yusuf, OM, Zar, HJ, Zhang, L., Zhong, N, Zernotti, ME, Zhanat, I, Zidarn, M, Zuberbier, T., Zubrinich, C, Zurkuhlen, A, Mercier, Jacques, Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Universitat Pompeu Fabra [Barcelona] (UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), IMIM-Hospital del Mar, Generalitat de Catalunya, Center of Research in Health Technologies and Information Systems (CINTESIS), Universidade do Porto = University of Porto, KYomed INNOV, Ghent University Hospital, Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Odense University Hospital [Odense, Denmark], Woolcock Institute of Medical Research [Sydney], The University of Sydney, Vall d'Hebron University Hospital [Barcelona], ProAR - FMB, Federal University of Bahia School of Medicine, European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA), University Hospitals Leuven [Leuven], Zentrum für Rhinologie und Allergologie [Wiesbaden, Germany], Division of Internal Medicine, Asthma and Allergy, Medical University of Łódź (MUL)-Barlicki University Hospital, Vilnius University [Vilnius], Clínica de Alergia- Asma y Pediatría, Hospital Medica Sur, Institute of Environmental Medicine, Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm]-Astrid Lindgren Children's Hospital, Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), Service de Pneumologie Allergologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris] (IP), Medical University of Warsaw - Poland, Department of Pulmonology, Manisa Celal Bayar University, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Center for Rhinology and Allergology Wiesbaden, University Hospital Mannheim, Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, Department of Allergy and Clinical Immunology, Faculty of Medicine-Transylvania University, Swiss Institute of Allergy and Asthma Research (SIAF), Universität Zürich [Zürich] = University of Zurich (UZH), Department Engineering Quimica (ICEMS), Aix Marseille Université (AMU), Istituto Nazionale di Fisica Nucleare, sezione di Bari (INFN, sezione di Bari), Istituto Nazionale di Fisica Nucleare (INFN), iQ4U consultants Ltd, Divisions of Human Genetics Infection, Inflammation and Repair, University of Southampton-School of Medicine, Department of Respiratory Medicine and Allergy, Department of Pathophysiology and Transplantation, Università degli Studi di Milano = University of Milan (UNIMI), Istituto di Geoscienze e Georisorse, Pavia, Institute of Neurobiology and Molecular Medicine, CNR, Rome, Italy and Department of Medicine-University of Naples Federico II = Università degli studi di Napoli Federico II, CHU Montpellier, Laboratoire National Henri Becquerel (LNHB), Département Métrologie Instrumentation & Information (DM2I), Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Département d'instrumentation Numérique (DIN (CEA-LIST)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Unité de Nutrition Humaine (UNH), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de recherche sur les mécanismes moléculaires et pharmacologiques de l’obstruction bronchique (LOBIP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Région Languedoc-Roussillon-Midi-Pyrénées, University of South Florida [Tampa] (USF), Chinese academy of sciences Sanya, Centres de Ressources et de Compétences de la Mucoviscidose [Montpellier] (CRCM [Montpellier]), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve-Service des Maladies Respiratoires, Laboratoire de Génie Informatique et d'Ingénierie de Production (LGI2P), IMT - MINES ALES (IMT - MINES ALES), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Department of Paediatrics, UCB Pharma, Colombes, CHU Strasbourg, Università degli Studi di Salerno = University of Salerno (UNISA), Hôpital Foch [Suresnes], Service de pneumologie [Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Informatique, Image, Intelligence Artificielle (I3A), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-IMT - MINES ALES (IMT - MINES ALES), Laboratoire Electronique, Informatique et Image [UMR6306] (Le2i), Université de Bourgogne (UB)-École Nationale Supérieure d'Arts et Métiers (ENSAM), Arts et Métiers Sciences et Technologies, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Center for Allergy and Immunology Research [Tbilisi], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Center for Turbulence Research [Stanford] (CTR), Stanford University, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), The Institute of Environmental Medicine [Stockholm] (IMM), Karolinska Institutet [Stockholm], Sysdiag-Modélisation et Ingénierie des Systèmes Complexes Biologiques pour le Diagnostic (SysDiag ), BIO-RAD-Centre National de la Recherche Scientifique (CNRS), Équipe de Recherche en Textes, Informatique, Multilinguisme (ERTIM), Institut National des Langues et Civilisations Orientales (Inalco), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Biomax Informatics AG, 'Federico II' University of Naples Medical School, Pneumology Department, Marius Nasta Institute of Pneumology, Epidémiologie Environnementale : Impact Sanitaire des Pollutions (EA 4064), Université Paris Descartes - Paris 5 (UPD5), Johns Hopkins University School of Medicine [Baltimore], CARSAT-LR, Montpellier, Dept. of Electronic Engineering, Chubu University, Institute for Solid State Physics, The University of Tokyo (UTokyo), Respiratory Medicine, Laboratoire de physique et chimie des nano-objets (LPCNO), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), CHU Grenoble, University of Cyprus [Nicosia] (UCY), Son Pisa Primary Care Centre, IB-Salut Balearic Health Service, Department of Computer Science [Haifa], University of Haifa [Haifa], University of Edinburgh, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Réseau National de Surveillance Aérobiologique (RNSA), CIRCE, Ctr Res Energy Resources & Consumpt, Zaragoza 50018, Spain, University of Turku, Evaluation et modélisation des effets thérapeutiques, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), ASA (Advanced Solution Accelerator) (Data management : Développement Back-Office, hébergement…), 34830 Jacou, Consiglio nazionale delle ricerche, Instituto di fisiologia clinica, McMaster University [Hamilton, Ontario], Department of Molecular Medicine and Surgery, UMR CNRS 8179, Université de Lille, Sciences et Technologies-Centre National de la Recherche Scientifique (CNRS), University Hospital of Cologne [Cologne], Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), ISGlobal, Barcelona, Spain, Universitat Pompeu Fabra (UPF), Barcelona, Spain, CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain, IMIM (Hospital del Mar Research Institute), Barcelona, Spain, CINTESIS, Center for Research in Health Technology and Information Systems, Faculdade de Medicina da Universidade do Porto, Porto, Portugal, Medida, Lda Porto, Porto, Portugal, KYomed INNOV, Montpellier, France, Upper Airways Research Laboratory, ENT Dept, Ghent University Hospital, Ghent, Belgium, MACVIA-France, Montpellier, France, Department of Dermatology and Allergy Centre, Odense University Hospital, Odense Research Center for Anaphylaxis (ORCA), Odense, Denmark, Woolcock Institute of Medical Research, University of Sydney and Woolcock Emphysema Centre and Sydney Local Health District, Glebe, NSW, Australia, Allergy Section, Department of Internal Medicine, Hospital Vall d'Hebron & ARADyAL Research Network, Barcelona, Spain, ProAR – Nucleo de Excelencia em Asma, Federal University of Bahia, Brasil and WHO GARD Planning Group, Salvador, Brazil, Department of Otorhinolaryngology, Amsterdam University Medical Centres, AMC, Amsterdam, Netherlands, Euforea, Brussels, Belgium, Department of Otorhinolaryngology, University Hospitals Leuven, Leuven, Belgium, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands, Servicio de Alergia e Immunologia, Clinica Santa Isabel, Buenos Aires, Argentina, Center for Rhinology and Allergology, Wiesbaden, Germany, Division of Internal Medicine, Asthma and Allergy, Barlicki University Hospital, Medical University of Lodz, Lodz, Poland, Department of Pathology, Faculty of Medicine, Institute of Biomedical Sciences, Vilnius University, Vilnius, Lithuania, Clinic of Chest diseases and Allergology, Faculty of Medicine, Institute of Clinical Medicine, Vilnius, Lithuania, Center of Excellence in Asthma and Allergy, Médica Sur Clinical Foundation and Hospital, México City, Mexico, Sachs' Children and Youth Hospital, Södersjukhuset, Stockholm, Sweden, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, Allergy and Clinical Immunology Unit, Department of Medical Sciences, University of Torino & Mauriziano Hospital, Torino, Italy, Institute of Medical Statistics, and Computational Biology, Medical Faculty, University of Cologne, Cologne, Germany, CRI-Clinical Research International-Ltd, Hamburg, Germany, Rhinology Unit & Smell Clinic, ENT Department, Hospital Clínic, University of Barcelona, Barcelona, Spain, Clinical & Experimental Respiratory Immunoallergy, IDIBAPS, CIBERES, University of Barcelona, Barcelona, Spain, Division of Infection, Immunity & Respiratory Medicine, Royal Manchester Children's Hospital, University of Manchester, Manchester, United Kingdom, Allergy Department, Pasteur Institute, Paris, France, Department of Prevention of Environmental Hazards and Allergology, Medical University of Warsaw, Warsaw, Poland, Department of General ORL, H&NS, Medical University of Graz, Graz, Austria, Skin and Allergy Hospital, Helsinki University Hospital, and University of Helsinki, Helsinki, Finland, Unit of Geriatric Immunoallergology, University of Bari Medical School, Bari, Italy, Department of Pulmonary Diseases, Faculty of Medicine, Celal Bayar University, Manisa, Turkey, University Hospital, Montpellier, France, INSERM U 1168, VIMA: Ageing and Chronic Diseases Epidemiological and Public Health Approaches, Villejuif, France, UMR-S 1168, Université Versailles St-Quentin-en-Yvelines, Versailles, France, Charité, Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin, Germany, Comprehensive Allergy Center, Department of Dermatology and Allergy, Berlin Institute of Health, Berlin, Germany, Department of Otorhinolaryngology, Head and Neck Surgery, Section of Rhinology and Allergy, University Hospital Marburg, Phillipps-Universität, Marburg, Germany, Universidade do Porto, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut Pasteur [Paris], University of Milan, University of Naples Federico II-CNR, Rome, Italy and Department of Medicine, Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Università degli Studi di Salerno (UNISA), CHU Toulouse [Toulouse]-Hôpital Larrey [Toulouse], CHU Toulouse [Toulouse], Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Arts et Métiers (ENSAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, University of Helsinki, Service d'Allergologie pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Astrophysique Interprétation Modélisation (AIM (UMR_7158 / UMR_E_9005 / UM_112)), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), University of Cyprus [Nicosia], Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Bedard, A., Anto, J. M., Fonseca, J. A., Arnavielhe, S., Bachert, C., Bedbrook, A., Bindslev-Jensen, C., Bosnic-Anticevich, S., Cardona, V., Cruz, A. A., Fokkens, W. J., Garcia-Aymerich, J., Hellings, P. W., Ivancevich, J. C., Klimek, L., Kuna, P., Kvedariene, V., Larenas-Linnemann, D., Melen, E., Monti, R., Mosges, R., Mullol, J., Papadopoulos, N. G., Pham-Thi, N., Samolinski, B., Tomazic, P. V., Toppila-Salmi, S., Ventura, M. T., Yorgancioglu, A., Bousquet, J., Pfaar, O., Basagana, X., Aberer, W., Agache, I., Akdis, C. A., Akdis, M., Aliberti, M. R., Almeida, R., Amat, F., Angles, R., Annesi-Maesano, I., Ansotegui, I. J., Arnavielle, S., Asayag, E., Asarnoj, A., Arshad, H., Avolio, F., Bacci, E., Baiardini, I., Barbara, C., Barbagallo, M., Baroni, I., Barreto, B. A., Bateman, E. D., Bedolla-Barajas, M., Bewick, M., Beghe, B., Bel, E. H., Bergmann, K. C., Bennoor, K. S., Benson, M., Bertorello, L., Bialoszewski, A. Z., Bieber, T., Bialek, S., Bjermer, L., Blain, H., Blasi, F., Blua, A., Bochenska Marciniak, M., Bogus-Buczynska, I., Boner, A. L., Bonini, M., Bonini, S., Bosse, I., Bouchard, J., Boulet, L. P., Bourret, R., Bousquet, P. J., Braido, F., Briedis, V., Brightling, C. E., Brozek, J., Bucca, C., Buhl, R., Buonaiuto, R., Panaitescu, C., Burguete Cabanas, M. T., Burte, E., Bush, A., Caballero-Fonseca, F., Caillaud, D., Caimmi, D., Calderon, M. A., Camargos, P. A. M., Camuzat, T., Canfora, G., Canonica, G. W., Carlsen, K. H., Carreiro-Martins, P., Carriazo, A. M., Carr, W., Cartier, C., Casale, T., Castellano, G., Cecchi, L., Cepeda, A. M., Chavannes, N. H., Chen, Y., Chiron, R., Chivato, T., Chkhartishvili, E., Chuchalin, A. G., Chung, K. F., Ciaravolo, M. M., Ciceran, A., Cingi, C., Ciprandi, G., Carvalho Coehlo, A. C., Colas, L., Colgan, E., Coll, J., Conforti, D., Constantinidis, J., Correia de Sousa, J., Cortes-Grimaldo, R. M., Corti, F., Costa, E., Costa-Dominguez, M. C., Courbis, A. L., Cox, L., Crescenzo, M., Custovic, A., Czarlewski, W., Dahlen, S. E., D'Amato, G., Dario, C., da Silva, J., Dauvilliers, Y., Darsow, U., De Blay, F., De Carlo, G., Dedeu, T., de Fatima Emerson, M., De Feo, G., De Vries, G., De Martino, B., Motta Rubini, N. P., Deleanu, D., Denburg, J. A., Devillier, P., Di Capua Ercolano, S., Di Carluccio, N., Didier, A., Dokic, D., Dominguez-Silva, M. G., Douagui, H., Dray, G., Dubakiene, R., Durham, S. R., Du Toit, G., Dykewicz, M. S., El-Gamal, Y., Eklund, P., Eller, E., Emuzyte, R., Farrell, J., Farsi, A., Ferreira de Mello, J., Ferrero, J., Fink-Wagner, A., Fiocchi, A., Fontaine, J. F., Forti, S., Fuentes-Perez, J. M., Galvez-Romero, J. L., Gamkrelidze, A., Garcia-Cobas, C. Y., Garcia-Cruz, M. H., Gemicioglu, B., Genova, S., Christoff, G., Gereda, J. E., Gerth van Wijk, R., Gomez, R. M., Gomez-Vera, J., Gonzalez Diaz, S., Gotua, M., Grisle, I., Guidacci, M., Guldemond, N. A., Gutter, Z., Guzman, M. A., Haahtela, T., Hajjam, J., Hernandez, L., Hourihane, J. O. '. B., Huerta-Villalobos, Y. R., Humbert, M., Iaccarino, G., Illario, M., Ispayeva, Z., Jares, E. J., Jassem, E., Johnston, S. L., Joos, G., Jung, K. S., Just, J., Jutel, M., Kaidashev, I., Kalayci, O., Kalyoncu, A. F., Karjalainen, J., Kardas, P., Keil, T., Keith, P. K., Khaitov, M., Khaltaev, N., Kleine-Tebbe, J., Kowalski, M. L., Kuitunen, M., Kull, I., Kupczyk, M., Krzych-Falta, E., Lacwik, P., Laune, D., Lauri, D., Lavrut, J., Le, L. T. T., Lessa, M., Levato, G., Li, J., Lieberman, P., Lipiec, A., Lipworth, B., Lodrup Carlsen, K. C., Louis, R., Lourenco, O., Luna-Pech, J. A., Magnan, A., Mahboub, B., Maier, D., Mair, A., Majer, I., Malva, J., Mandajieva, E., Manning, P., De Manuel Keenoy, E., Marshall, G. D., Masjedi, M. R., Maspero, J. F., Mathieu-Dupas, E., Matta Campos, J. J., Matos, A. L., Maurer, M., Mavale-Manuel, S., Mayora, O., Meco, C., Medina-Avalos, M. A., Melo-Gomes, E., Meltzer, E. O., Menditto, E., Mercier, J., Miculinic, N., Mihaltan, F., Milenkovic, B., Moda, G., Mogica-Martinez, M. D., Mohammad, Y., Momas, I., Montefort, S., Mora Bogado, D., Morais-Almeida, M., Morato-Castro, F. F., Mota-Pinto, A., Moura Santo, P., Munter, L., Muraro, A., Murray, R., Naclerio, R., Nadif, R., Nalin, M., Napoli, L., Namazova-Baranova, L., Neffen, H., Niedeberger, V., Nekam, K., Neou, A., Nieto, A., Nogueira-Silva, L., Nogues, M., Novellino, E., Nyembue, T. D., O'Hehir, R. E., Odzhakova, C., Ohta, K., Okamoto, Y., Okubo, K., Onorato, G. L., Ortega Cisneros, M., Ouedraogo, S., Pali-Scholl, I., Palkonen, S., Panzner, P., Park, H. S., Papi, A., Passalacqua, G., Paulino, E., Pawankar, R., Pedersen, S., Pepin, J. L., Pereira, A. M., Persico, M., Phillips, J., Picard, R., Pigearias, B., Pin, I., Pitsios, C., Plavec, D., Pohl, W., Popov, T. A., Portejoie, F., Potter, P., Pozzi, A. C., Price, D., Prokopakis, E. P., Puy, R., Pugin, B., Pulido Ross, R. E., Przemecka, M., Rabe, K. F., Raciborski, F., Rajabian-Soderlund, R., Reitsma, S., Ribeirinho, I., Rimmer, J., Rivero-Yeverino, D., Rizzo, J. A., Rizzo, M. C., Robalo-Cordeiro, C., Rodenas, F., Rodo, X., Rodriguez Gonzalez, M., Rodriguez-Manas, L., Rolland, C., Rodrigues Valle, S., Roman Rodriguez, M., Romano, A., Rodriguez-Zagal, E., Rolla, G., Roller-Wirnsberger, R. E., Romano, M., Rosado-Pinto, J., Rosario, N., Rottem, M., Ryan, D., Sagara, H., Salimaki, J., Sanchez-Borges, M., Sastre-Dominguez, J., Scadding, G. K., Schunemann, H. J., Scichilone, N., Schmid-Grendelmeier, P., Sarquis Serpa, F., Shamai, S., Sheikh, A., Sierra, M., Simons, F. E. R., Siroux, V., Sisul, J. C., Skrindo, I., Sole, D., Somekh, D., Sondermann, M., Sooronbaev, T., Sova, M., Sorensen, M., Sorlini, M., Spranger, O., Stellato, C., Stelmach, R., Stukas, R., Sunyer, J., Strozek, J., Szylling, A., Tebyrica, J. N., Thibaudon, M., To, T., Todo-Bom, A., Trama, U., Triggiani, M., Suppli Ulrik, C., Urrutia-Pereira, M., Valenta, R., Valero, A., Valiulis, A., Valovirta, E., van Eerd, M., van Ganse, E., van Hage, M., Vandenplas, O., Vezzani, G., Vasankari, T., Vatrella, A., Verissimo, M. T., Viart, F., Viegi, G., Vicheva, D., Vontetsianos, T., Wagenmann, M., Walker, S., Wallace, D., Wang, D. Y., Waserman, S., Werfel, T., Westman, M., Wickman, M., Williams, D. M., Williams, S., Wilson, N., Wright, J., Wroczynski, P., Yakovliev, P., Yawn, B. P., Yiallouros, P. K., Yusuf, O. M., Zar, H. J., Zhang, L., Zhong, N., Zernotti, M. E., Zhanat, I., Zidarn, M., Zuberbier, T., Zubrinich, C., Zurkuhlen, A., HESAM Université (HESAM)-HESAM Université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Universitat Pompeu Fabra [Barcelona]-Catalunya ministerio de salud, Universidade do Porto [Porto], Kyomed, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Universitat Pompeu Fabra [Barcelona], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Service des Maladies Respiratoires, Hôpital Arnaud de Villeneuve-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Dermatology [Graz, Austria], Medical University Graz, University of Zürich [Zürich] (UZH), National Institute for Nuclear Physics (INFN), Institut Jean Lamour (IJL), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Clermont Université-Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Recherche Agronomique (INRA), University of South Florida (USF), University of Salerno (UNISA), CHU Toulouse [Toulouse]-Hôpital Larrey, Institut Mines-Télécom [Paris] (IMT), Center for Turbulence Research (CTR), Stanford University [Stanford], Service d'allergologie [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), The University of Tokyo, Sondra, CentraleSupélec, Université Paris-Saclay (SONDRA), ONERA-CentraleSupélec-Université Paris-Saclay, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), RNSA, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Ear, Nose and Throat, AII - Inflammatory diseases, Pulmonology, CNR, Rome, Italy and Department of Medicine-University of Naples Federico II, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, UCL - (MGD) Service de pneumologie, Bedard A., Anto J.M., Fonseca J.A., Arnavielhe S., Bachert C., Bedbrook A., Bindslev-Jensen C., Bosnic-Anticevich S., Cardona V., Cruz A.A., Fokkens W.J., Garcia-Aymerich J., Hellings P.W., Ivancevich J.C., Klimek L., Kuna P., Kvedariene V., Larenas-Linnemann D., Melen E., Monti R., Mosges R., Mullol J., Papadopoulos N.G., Pham-Thi N., Samolinski B., Tomazic P.V., Toppila-Salmi S., Ventura M.T., Yorgancioglu A., Bousquet J., Pfaar O., Basagana X., Aberer W., Agache I., Akdis C.A., Akdis M., Aliberti M.R., Almeida R., Amat F., Angles R., Annesi-Maesano I., Ansotegui I.J., Arnavielle S., Asayag E., Asarnoj A., Arshad H., Avolio F., Bacci E., Baiardini I., Barbara C., Barbagallo M., Baroni I., Barreto B.A., Bateman E.D., Bedolla-Barajas M., Bewick M., Beghe B., Bel E.H., Bergmann K.C., Bennoor K.S., Benson M., Bertorello L., Bialoszewski A.Z., Bieber T., Bialek S., Bjermer L., Blain H., Blasi F., Blua A., Bochenska Marciniak M., Bogus-Buczynska I., Boner A.L., Bonini M., Bonini S., Bosse I., Bouchard J., Boulet L.P., Bourret R., Bousquet P.J., Braido F., Briedis V., Brightling C.E., Brozek J., Bucca C., Buhl R., Buonaiuto R., Panaitescu C., Burguete Cabanas M.T., Burte E., Bush A., Caballero-Fonseca F., Caillaud D., Caimmi D., Calderon M.A., Camargos P.A.M., Camuzat T., Canfora G., Canonica G.W., Carlsen K.H., Carreiro-Martins P., Carriazo A.M., Carr W., Cartier C., Casale T., Castellano G., Cecchi L., Cepeda A.M., Chavannes N.H., Chen Y., Chiron R., Chivato T., Chkhartishvili E., Chuchalin A.G., Chung K.F., Ciaravolo M.M., Ciceran A., Cingi C., Ciprandi G., Carvalho Coehlo A.C., Colas L., Colgan E., Coll J., Conforti D., Constantinidis J., Correia de Sousa J., Cortes-Grimaldo R.M., Corti F., Costa E., Costa-Dominguez M.C., Courbis A.L., Cox L., Crescenzo M., Custovic A., Czarlewski W., Dahlen S.E., D'Amato G., Dario C., da Silva J., Dauvilliers Y., Darsow U., De Blay F., De Carlo G., Dedeu T., de Fatima Emerson M., De Feo G., De Vries G., De Martino B., Motta Rubini N.P., Deleanu D., Denburg J.A., Devillier P., Di Capua Ercolano S., Di Carluccio N., Didier A., Dokic D., Dominguez-Silva M.G., Douagui H., Dray G., Dubakiene R., Durham S.R., Du Toit G., Dykewicz M.S., El-Gamal Y., Eklund P., Eller E., Emuzyte R., Farrell J., Farsi A., Ferreira de Mello J., Ferrero J., Fink-Wagner A., Fiocchi A., Fontaine J.F., Forti S., Fuentes-Perez J.M., Galvez-Romero J.L., Gamkrelidze A., Garcia-Cobas C.Y., Garcia-Cruz M.H., Gemicioglu B., Genova S., Christoff G., Gereda J.E., Gerth van Wijk R., Gomez R.M., Gomez-Vera J., Gonzalez Diaz S., Gotua M., Grisle I., Guidacci M., Guldemond N.A., Gutter Z., Guzman M.A., Haahtela T., Hajjam J., Hernandez L., Hourihane J.O.'.B., Huerta-Villalobos Y.R., Humbert M., Iaccarino G., Illario M., Ispayeva Z., Jares E.J., Jassem E., Johnston S.L., Joos G., Jung K.S., Just J., Jutel M., Kaidashev I., Kalayci O., Kalyoncu A.F., Karjalainen J., Kardas P., Keil T., Keith P.K., Khaitov M., Khaltaev N., Kleine-Tebbe J., Kowalski M.L., Kuitunen M., Kull I., Kupczyk M., Krzych-Falta E., Lacwik P., Laune D., Lauri D., Lavrut J., Le L.T.T., Lessa M., Levato G., Li J., Lieberman P., Lipiec A., Lipworth B., Lodrup Carlsen K.C., Louis R., Lourenco O., Luna-Pech J.A., Magnan A., Mahboub B., Maier D., Mair A., Majer I., Malva J., Mandajieva E., Manning P., De Manuel Keenoy E., Marshall G.D., Masjedi M.R., Maspero J.F., Mathieu-Dupas E., Matta Campos J.J., Matos A.L., Maurer M., Mavale-Manuel S., Mayora O., Meco C., Medina-Avalos M.A., Melo-Gomes E., Meltzer E.O., Menditto E., Mercier J., Miculinic N., Mihaltan F., Milenkovic B., Moda G., Mogica-Martinez M.D., Mohammad Y., Momas I., Montefort S., Mora Bogado D., Morais-Almeida M., Morato-Castro F.F., Mota-Pinto A., Moura Santo P., Munter L., Muraro A., Murray R., Naclerio R., Nadif R., Nalin M., Napoli L., Namazova-Baranova L., Neffen H., Niedeberger V., Nekam K., Neou A., Nieto A., Nogueira-Silva L., Nogues M., Novellino E., Nyembue T.D., O'Hehir R.E., Odzhakova C., Ohta K., Okamoto Y., Okubo K., Onorato G.L., Ortega Cisneros M., Ouedraogo S., Pali-Scholl I., Palkonen S., Panzner P., Park H.S., Papi A., Passalacqua G., Paulino E., Pawankar R., Pedersen S., Pepin J.L., Pereira A.M., Persico M., Phillips J., Picard R., Pigearias B., Pin I., Pitsios C., Plavec D., Pohl W., Popov T.A., Portejoie F., Potter P., Pozzi A.C., Price D., Prokopakis E.P., Puy R., Pugin B., Pulido Ross R.E., Przemecka M., Rabe K.F., Raciborski F., Rajabian-Soderlund R., Reitsma S., Ribeirinho I., Rimmer J., Rivero-Yeverino D., Rizzo J.A., Rizzo M.C., Robalo-Cordeiro C., Rodenas F., Rodo X., Rodriguez Gonzalez M., Rodriguez-Manas L., Rolland C., Rodrigues Valle S., Roman Rodriguez M., Romano A., Rodriguez-Zagal E., Rolla G., Roller-Wirnsberger R.E., Romano M., Rosado-Pinto J., Rosario N., Rottem M., Ryan D., Sagara H., Salimaki J., Sanchez-Borges M., Sastre-Dominguez J., Scadding G.K., Schunemann H.J., Scichilone N., Schmid-Grendelmeier P., Sarquis Serpa F., Shamai S., Sheikh A., Sierra M., Simons F.E.R., Siroux V., Sisul J.C., Skrindo I., Sole D., Somekh D., Sondermann M., Sooronbaev T., Sova M., Sorensen M., Sorlini M., Spranger O., Stellato C., Stelmach R., Stukas R., Sunyer J., Strozek J., Szylling A., Tebyrica J.N., Thibaudon M., To T., Todo-Bom A., Trama U., Triggiani M., Suppli Ulrik C., Urrutia-Pereira M., Valenta R., Valero A., Valiulis A., Valovirta E., van Eerd M., van Ganse E., van Hage M., Vandenplas O., Vezzani G., Vasankari T., Vatrella A., Verissimo M.T., Viart F., Viegi G., Vicheva D., Vontetsianos T., Wagenmann M., Walker S., Wallace D., Wang D.Y., Waserman S., Werfel T., Westman M., Wickman M., Williams D.M., Williams S., Wilson N., Wright J., Wroczynski P., Yakovliev P., Yawn B.P., Yiallouros P.K., Yusuf O.M., Zar H.J., Zhang L., Zhong N., Zernotti M.E., Zhanat I., Zidarn M., Zuberbier T., Zubrinich C., and Zurkuhlen A.
Subjects: 0301 basic medicine, SYMPTOMS, Smart phone, Allergy, Escala visual analógica, INNOVATION, [SDV]Life Sciences [q-bio], Medical and Health Sciences, Correlation, visual analogue scale, 0302 clinical medicine, Quality of life, Visual analogue scale, QUALITY-OF-LIFE, Màscares, Immunology and Allergy, score, Nose, Rinitis, Rhinitis, PRODUCTIVITY COSTS, asthma, MASK, rhinitis, Score, Explained variation, Response Variability, Mobile Applications, ALLERGIC RHINITIS, rhiniti, medicine.anatomical_structure, TRIALS, Rinite, 1107 Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Smartphone, medicine.medical_specialty, MASK study group, Immunology, MACVIA-ARIA, 03 medical and health sciences, Allergic, medicine, Humans, TECHNOLOGY, IMMUNOTHERAPY, Asma, Asthma, business.industry, Rhinitis, Allergic, medicine.disease, RHINOCONJUNCTIVITIS, 030104 developmental biology, 030228 respiratory system, 3121 General medicine, internal medicine and other clinical medicine, Physical therapy, Clinical Medicine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background: In allergic rhinitis, a relevant outcome providing information on the effectiveness of interventions is needed. In MASK-air (Mobile Airways Sentinel Network), a visual analogue scale (VAS) for work is used as a relevant outcome. This study aimed to assess the performance of the work VAS work by comparing VAS work with other VAS measurements and symptom-medication scores obtained concurrently. Methods: All consecutive MASK-air users in 23 countries from 1 June 2016 to 31 October 2018 were included (14 189 users; 205 904 days). Geolocalized users self-assessed daily symptom control using the touchscreen functionality on their smart phone to click on VAS scores (ranging from 0 to 100) for overall symptoms (global), nose, eyes, asthma and work. Two symptom-medication scores were used: the modified EAACI CSMS score and the MASK control score for rhinitis. To assess data quality, the intra-individual response variability (IRV) index was calculated. Results: A strong correlation was observed between VAS work and other VAS. The highest levels for correlation with VAS work and variance explained in VAS work were found with VAS global, followed by VAS nose, eye and asthma. In comparison with VAS global, the mCSMS and MASK control score showed a lower correlation with VAS work. Results are unlikely to be explained by a low quality of data arising from repeated VAS measures. Conclusions: VAS work correlates with other outcomes (VAS global, nose, eye and asthma) but less well with a symptom-medication score. VAS work should be considered as a potentially useful AR outcome in intervention studies. © 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.
Published: 2020

23. The Human Cytomegalovirus Protein UL116 Interacts with the Viral Endoplasmic-Reticulum-Resident Glycoprotein UL148 and Promotes the Incorporation of gH/gL Complexes into Virions

Author: Diego Amendola, Mohammed N. A. Siddiquey, Marcello Merola, Qin Yu, Brent J. Ryckman, Dong Yu, Jeremy P. Kamil, Eric P. Schultz, Domenico Maione, Jean-Marc Lanchy, Giacomo Vezzani, Siddiquey, M. N. A., Schultz, E. P., Yu, Q., Amendola, D., Vezzani, G., Yu, D., Maione, D., Lanchy, J. -M., Ryckman, B. J., Merola, M., and Kamil, J. P.
Subjects: Cytomegalovirus Infection, viruses, Cytomegalovirus, chemistry.chemical_compound, Bioassembly, HEK293 Cell, Viral Envelope Proteins, Human herpesviruse, Alkaloid, Enzyme Inhibitor, Enzyme Inhibitors, Viral Fusion Protein, chemistry.chemical_classification, Membrane Glycoproteins, Viral Envelope Protein, Endoplasmic Reticulum Stress, Cell biology, Kifunensine, Cytomegalovirus Infections, Membrane Glycoprotein, Human, Gene Expression Regulation, Viral, Immunology, Biology, Endoplasmic-reticulum-associated protein degradation, Tropism, Microbiology, Cell Line, Alkaloids, Viral entry, Virology, Humans, Endoplasmic Reticulum Stre, Herpesviruse, Structure and Assembly, Endoplasmic reticulum, HEK 293 cells, Cytomegaloviru, Virion structure, ERAD, Virus Internalization, Membrane glycoproteins, HEK293 Cells, chemistry, Cell culture, Insect Science, biology.protein, Glycoprotein, Viral Fusion Proteins
Abstract: Heterodimers of glycoproteins H (gH) and L (gL) comprise a basal element of the viral membrane fusion machinery conserved across herpesviruses. In human cytomegalovirus (HCMV), the glycoprotein UL116 assembles onto gH at a position similar to that occupied by gL, forming a heterodimer that is incorporated into virions. Here, we show that UL116 promotes the expression of gH/gL complexes and is required for the efficient production of infectious cell-free virions. UL116-null mutants show a 10-fold defect in production of infectious cell-free virions from infected fibroblasts and epithelial cells. This defect is accompanied by reduced expression of two disulfide-linked gH/gL complexes that play crucial roles in viral entry: the heterotrimer of gH/gL with glycoprotein O (gO) and the pentameric complex of gH/gL with UL128, UL130, and UL131. Kifunensine, a mannosidase inhibitor that interferes with endoplasmic reticulum (ER)-associated degradation (ERAD) of terminally misfolded glycoproteins, restored levels of gH, gL, and gO in UL116-null-infected cells, indicating that constituents of HCMV gH complexes are unstable in the absence of UL116. Further, we find that gH/UL116 complexes are abundant in virions, since a major gH species not covalently linked to other glycoproteins, which has long been observed in the literature, is detected from wild-type but not UL116-null virions. Interestingly, UL116 coimmunoprecipitates with UL148, a viral ER-resident glycoprotein that attenuates ERAD of gO, and we observe elevated levels of UL116 in UL148-null virions. Collectively, our findings argue that UL116 is a chaperone for gH that supports the assembly, maturation, and incorporation of gH/gL complexes into virions. IMPORTANCE HCMV is a betaherpesvirus that causes dangerous opportunistic infections in immunocompromised patients as well as in the immune-naive fetus and preterm infants. The potential of the virus to enter new host cells is governed in large part by two alternative viral glycoprotein H (gH)/glycoprotein L (gL) complexes that play important roles in entry: gH/gL/gO and gH/gL/UL128-131. A recently identified virion gH complex, comprised of gH bound to UL116, adds a new layer of complexity to the mechanisms that contribute to HCMV infectivity. Here, we show that UL116 promotes the expression of gH/gL complexes and that UL116 interacts with the viral ER-resident glycoprotein UL148, a factor that supports the expression of gH/gL/gO. Overall, our results suggest that UL116 is a chaperone for gH. These findings have important implications for understanding HCMV cell tropism as well as for the development of vaccines against the virus.
Published: 2021

24. Characterization of pUL5, an HCMV protein interacting with the cellular protein IQGAP1

Author: Mirko Cortese, Giacomo Vezzani, Maria Giuliani, Diego Amendola, Rossella Ferranti, Giulia Anselmi, Yasushi Uematsu, Luca Bruno, Nicola Pacchiani, Marcello Merola, Michela Gentile, Domenico Maione, Romina D'Aurizio, Anselmi, G., Giuliani, M., Vezzani, G., Ferranti, R., Gentile, M., Cortese, M., Amendola, D., Pacchiani, N., D'Aurizio, R., Bruno, L., Uematsu, Y., Merola, M., Maione, D., Anselmi, Giulia, Giuliani, Maria, Vezzani, Giacomo, Ferranti, Rossella, Gentile, Michela, Cortese, Mirko, Amendola, Diego, Pacchiani, Nicola, D'Aurizio, Romina, Bruno, Luca, Uematsu, Yasushi, Merola, Marcello, and Maione, Domenico
Subjects: Human cytomegalovirus, Gene Expression Regulation, Viral, Coding potential, Transcription, Genetic, Cytomegalovirus, Biology, Recombinant virus, medicine.disease_cause, UL5 isoforms, Genome, UL5 Non-structural protein Coding potential UL5 isoforms Internal AUG IQGAP1, Herpesviridae, Cell Line, Gene product, 03 medical and health sciences, Open Reading Frames, Viral Proteins, Non-structural protein, Western blot, IQGAP1, Virology, medicine, Humans, Internal AUG, Amino Acid Sequence, Cells, Cultured, 030304 developmental biology, 0303 health sciences, medicine.diagnostic_test, 030302 biochemistry & molecular biology, medicine.disease, Molecular biology, Human cytomegaloviru, Open reading frame, Protein Transport, UL5, Membrane protein, ras GTPase-Activating Proteins, Cytomegalovirus Infections, Host-Pathogen Interactions, RNA, Viral, Protein Binding
Abstract: Among the Herpesviridae, human cytomegalovirus (HCMV) owns the largest genome and displays a huge coding potential. Here, we characterized the UL5 gene product (pUL5) of the clinical isolate TR strain. The protein was predicted as a 166-amino-acid membrane protein with a theoretical mass of 19 kDa. Recombinant virus expressing pUL5 with a tag allowed the identification of two pUL5 non-glycosylated species of approximately 19 and 9 kDa, expressed with early and late kinetic respectively. Experiments in infection confirmed that the lower molecular weight species was translated from an internal ATG in the UL5 open reading frame. Confocal microscopy analysis showed that pUL5 localized within the assembly compartment, but is not incorporated in the virion, as shown by Western blot on purified viral particles. Finally, pull-down experiments coupled with mass spectrometry analysis identified IQGAP1 as a pUL5 interactor, giving new hints on possible roles of pUL5 during HCMV infection.
Published: 2020

25. Chromosome 14 deletions, rings, and epilepsy genes: A riddle wrapped in a mystery inside an enigma

Author: Alessandro Vaisfeld, Giuseppe Gobbi, Serena Spartano, Giovanni Neri, and Annamaria Vezzani
Subjects: Cytoplasmic Dyneins, Ribonuclease III, 0301 basic medicine, Drug Resistant Epilepsy, Mutation, Missense, Vesicular Transport Proteins, Nerve Tissue Proteins, Molecular evidence, Biology, Ring 14 syndrome, Ring (chemistry), Retina, Craniofacial Abnormalities, DEAD-box RNA Helicases, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Chromosome (genetic algorithm), Intellectual Disability, Presenilin-1, medicine, Humans, Ring Chromosomes, Deletion syndrome, Eye Abnormalities, Gene, Chromosomes, Human, Pair 14, Genetics, Otx Transcription Factors, Breakpoint, Nuclear Proteins, Forkhead Transcription Factors, medicine.disease, DNA-Binding Proteins, Phenotype, 030104 developmental biology, Neurology, Microcephaly, Neurology (clinical), Chromosome Deletion, Carrier Proteins, 030217 neurology & neurosurgery, Transcription Factors
Abstract: The ring 14 syndrome is a rare condition caused by the rearrangement of one chromosome 14 into a ring-like structure. The formation of the ring requires two breakpoints and loss of material from the short and long arms of the chromosome. Like many other chromosome syndromes, it is characterized by multiple congenital anomalies and developmental delays. Typical of the condition are retinal anomalies and drug-resistant epilepsy. These latter manifestations are not found in individuals who are carriers of comparable 14q deletions without formation of a ring (linear deletions). To find an explanation for this apparent discrepancy and gain insight into the mechanisms leading to seizures, we reviewed and compared literature cases of both ring and linear deletion syndrome with respect to both their clinical manifestations and the role and function of potentially epileptogenic genes. Knowledge of the epilepsy-related genes in chromosome 14 is an important premise for the search of new and effective drugs to combat seizures. Current clinical and molecular evidence is not sufficient to explain the known discrepancies between ring and linear deletions.
Published: 2020

26. Pregnancy-related reference intervals for serum thyrotropin based on real-life clinical data

Author: Tommaso Fasano, Silvia Vezzani, Cristina Preda, Antonio Vitiello, Luigi Vecchia, Alessandra Polese, Simone Canovi, Clara Schiatti, Giuseppina Comitini, Michele Zini, Lorenzo Aguzzoli, Andrea Frasoldati, and Marco Foracchia
Subjects: Adult, endocrine system, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Population, Thyrotropin, Physiology, 030209 endocrinology & metabolism, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Pregnancy, Reference Values, Humans, Medicine, education, education.field_of_study, 030219 obstetrics & reproductive medicine, business.industry, Thyroid, Obstetrics and Gynecology, medicine.disease, Reference intervals, medicine.anatomical_structure, Female, Pregnancy Trimesters, business, hormones, hormone substitutes, and hormone antagonists, Homeostasis
Abstract: During pregnancy, thyroid homeostasis is physiologically modified, leading to altered levels of thyrotropin (TSH): hence, the adoption of pregnancy-related, population- and method-specific reference ranges is recommended. This monocentric and retrospective study was conducted to establish local pregnancy-related reference intervals for serum TSH in singleton pregnant women using real-life clinical data.We included women who measured serum TSH during pregnancy at our Laboratory over six years, excluding pregnant women with current or past history of thyroid disease, pituitary or autoimmune diseases, use of medications known to influence thyroid function, multiple and/or pathological pregnancies, BMI30 Kg/mWe retrieved a total of 3744 TSH results. Reference limits (90% confidence intervals) for TSH (in mIU/L) are: first trimester 0.09 (0.06-0.12) - 3.16 (3.05-3.29); second trimester 0.25 (0.11-0.30) - 3.55 (3.34-3.73); third trimester 0.42 (0.15-0.48) - 3.93 (3.80-4.08).In conclusion, real-life clinical data could be used to establish or verify local reference intervals for TSH in pregnant women: this may reduce the risk of misclassification of pregnant women undergoing thyroid function testing.
Published: 2020

27. HMGB1 is increased in adolescents with polycystic ovary syndrome (PCOS) and decreases after treatment with myo-inositol (MYO) in combination with alpha-lipoic acid (ALA)

Author: Sergio Amarri, Pietro Lazzeroni, Anna Maria Fulghesu, Maria E. Street, Francesca Cirillo, Gabriele Tridenti, Cecilia Catellani, Chiara Sartori, Cristina Vezzani, and Eleonora Madeddu
Subjects: medicine.medical_specialty, Adolescent, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Alpha-Lipoic Acid, chemical and pharmacologic phenomena, 030209 endocrinology & metabolism, HMGB1, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Internal medicine, medicine, Humans, Testosterone, Inositol, HMGB1 Protein, Ovarian Reserve, 030219 obstetrics & reproductive medicine, Estradiol, Thioctic Acid, biology, business.industry, Polycystic ovary syndrome (PCOS), Ovary, nutritional and metabolic diseases, Obstetrics and Gynecology, Luteinizing Hormone, medicine.disease, female genital diseases and pregnancy complications, Pathophysiology, Treatment Outcome, chemistry, biology.protein, Drug Therapy, Combination, Female, business, After treatment, Polycystic Ovary Syndrome
Abstract: PCOS treatment should be based on pathophysiology. High-mobility-group-box-1 (HMGB1) was shown to increase in PCOS patients as a consequence of reduced cystic-fibrosis-transmembrane-conductance-regulator (CFTR) expression in the ovary, and was associated with insulin resistance and inflammation, both features of PCOS. Inositols and ALA derivatives could have positive effects on insulin sensitivity, reduce androgens, and improve ovulation rhythm. The aim of this study was to verify changes in HMGB1, in metabolic and endocrine parameters in adolescents with PCOS compared with controls and after treatment with a combination of MYO + ALA. Twenty-three PCOS adolescents and 21 controls matched for age and BMI were enrolled. In all subjects, metabolic and hormonal parameters were assayed. Homeostatic index (HOMA-IR) and the triglyceride/HDL-cholesterol ratio were calculated. Ovarian volumes were evaluated. Patients were treated with MYO + ALA for 6 months. HMGB1 was measured using a specific ELISA assay. HMGB1 was increased in PCOS compared with controls (19.76 ± 5.99 versus 5.65 ± 1.88 ng/ml
Published: 2020

28. Sex difference in human olfactory sensitivity is associated with plasma adiponectin

Author: Daniela M Pfabigan, Cecilia Vezzani, Per Medbøe Thorsby, and Uta Sailer
Subjects: Leptin, Male, Behavioral Neuroscience, Sex Characteristics, Endocrinology, Endocrine and Autonomic Systems, digestive, oral, and skin physiology, Appetite, Humans, Female, Adiponectin, Ghrelin
Abstract: Energy deprivation as well as hormones that regulate appetite and eating can influence olfactory function. This study investigated olfactory sensitivity for a food-related and a non-food odour prior to and after a meal, and its relationship to the energy-regulating hormones ghrelin and adiponectin.The olfactory sensitivity for orange and rose (PEA) odour in healthy, normal-weight volunteers (19 women, 45 men, 1 undisclosed individual) was not affected by the consumption of a meal. Olfactory sensitivity was not associated with concentrations of circulating ghrelin. However, olfactory sensitivity was higher for women than for men, indicating better olfactory performance. This difference between women and men was related to concentrations of plasma adiponectin, an adipose-specific hormone.Adiponectin may thus explain why sex differences in olfactory sensitivity emerge, and may also account for some of the inconsistencies in previous findings on sex differences. Our findings add to the limited literature on the impact of stomach and adipose tissue-derived hormones on olfactory sensitivity. Further studies are needed to establish a causal link between circulating adiponectin and a sex difference in olfactory sensitivity.
Published: 2022

29. Clinical risk scores for the early prediction of severe outocomes in patients hospitalized for COVID-19: comment

Author: Rossio R., Tettamanti M., Nobili A., Harari S., Mannucci P. M., Bandera A., Peyvandi F., Bosari S., Scudeller L., Fusetti G., Rusconi L., Dell'Orto S., Prati D., Valenti L., Giovannelli S., Manunta M., Lamorte G., Ferrari F., Gori A., Muscatello A., Mangioni D., Alagna L., Bozzi G., Lombardi A., Ungaro R., Ancona G., Zuglian G., Bolis M., Iannotti N., Ludovisi S., Comelli A., Renisi G., Biscarini S., Castelli V., Palomba E., Fava M., Fortina V., Peri C. A., Saltini P., Viero G., Itri T., Ferroni V., Pastore V., Massafra R., Liparoti A., Muheberimana T., Giommi A., Bianco R., De Azevedo R. M., Chitani G. E., Gualtierotti R., Ferrari B., Boasi N., Pagliaro E., Massimo C., De Caro M., Giachi A., Montano N., Vigone B., Bellocchi C., Carandina A., Fiorelli E., Melli V., Tobaldini E., Blasi F., Aliberti S., Spotti M., Terranova L., Misuraca S., D'Adda A., Fiore S. D., Di Pasquale M., Mantero M., Contarini M., Ori M., Morlacchi L., Rossetti V., Gramegna A., Pappalettera M., Cavallini M., Buscemi A., Vicenzi M., Rota I., Costantino G., Solbiati M., Furlan L., Mancarella M., Colombo G., Fanin A., Passarella M., Monzani V., Canetta C., Rovellini A., Barbetta L., Billi F., Folli C., Accordino S., Maira D., Hu C. M., Motta I., Scaramellini N., Fracanzani A. L., Lombardi R., Cespiati A., Cesari M., Lucchi T., Proietti M., Calcaterra L., Mandelli C., Coppola C., Cerizza A., Pesenti A. M., Grasselli G., Galazzi A., Monti I., Galbussera A. A., Crisafulli E., Girelli D., Maroccia A., Gabbiani D., Busti F., Vianello A., Biondan M., Sartori F., Faverio P., Pesci A., Zucchetti S., Bonfanti P., Rossi M., Beretta I., Spolti A., Elia D., Cassandro R., Caminati A., Cipollone F., Guagnano M. T., D'Ardes D., Rossi I., Vezzani F., Spanevello A., Cherubino F., Visca D., Contoli M., Papi A., Morandi L., Battistini N., Moreo G. L., Iannuzzi P., Fumagalli D., Leone S., Rossio, R, Tettamanti, M, Nobili, A, Harari, S, Mannucci, P, Bandera, A, Peyvandi, F, Bosari, S, Scudeller, L, Fusetti, G, Rusconi, L, Dell'Orto, S, Prati, D, Valenti, L, Giovannelli, S, Manunta, M, Lamorte, G, Ferrari, F, Gori, A, Muscatello, A, Mangioni, D, Alagna, L, Bozzi, G, Lombardi, A, Ungaro, R, Ancona, G, Zuglian, G, Bolis, M, Iannotti, N, Ludovisi, S, Comelli, A, Renisi, G, Biscarini, S, Castelli, V, Palomba, E, Fava, M, Fortina, V, Peri, C, Saltini, P, Viero, G, Itri, T, Ferroni, V, Pastore, V, Massafra, R, Liparoti, A, Muheberimana, T, Giommi, A, Bianco, R, De Azevedo, R, Chitani, G, Gualtierotti, R, Ferrari, B, Boasi, N, Pagliaro, E, Massimo, C, De Caro, M, Giachi, A, Montano, N, Vigone, B, Bellocchi, C, Carandina, A, Fiorelli, E, Melli, V, Tobaldini, E, Blasi, F, Aliberti, S, Spotti, M, Terranova, L, Misuraca, S, D'Adda, A, Fiore, S, Di Pasquale, M, Mantero, M, Contarini, M, Ori, M, Morlacchi, L, Rossetti, V, Gramegna, A, Pappalettera, M, Cavallini, M, Buscemi, A, Vicenzi, M, Rota, I, Costantino, G, Solbiati, M, Furlan, L, Mancarella, M, Colombo, G, Fanin, A, Passarella, M, Monzani, V, Canetta, C, Rovellini, A, Barbetta, L, Billi, F, Folli, C, Accordino, S, Maira, D, Hu, C, Motta, I, Scaramellini, N, Fracanzani, A, Lombardi, R, Cespiati, A, Cesari, M, Lucchi, T, Proietti, M, Calcaterra, L, Mandelli, C, Coppola, C, Cerizza, A, Pesenti, A, Grasselli, G, Galazzi, A, Monti, I, Galbussera, A, Crisafulli, E, Girelli, D, Maroccia, A, Gabbiani, D, Busti, F, Vianello, A, Biondan, M, Sartori, F, Faverio, P, Pesci, A, Zucchetti, S, Bonfanti, P, Rossi, M, Beretta, I, Spolti, A, Elia, D, Cassandro, R, Caminati, A, Cipollone, F, Guagnano, M, D'Ardes, D, Rossi, I, Vezzani, F, Spanevello, A, Cherubino, F, Visca, D, Contoli, M, Papi, A, Morandi, L, Battistini, N, Moreo, G, Iannuzzi, P, Fumagalli, D, and Leone, S
Subjects: Male, Outcome Assessment, Disease, 030204 cardiovascular system & hematology, Respiratory failure, 0302 clinical medicine, Risk Factors, Epidemiology, Early prediction, Outcome Assessment, Health Care, 030212 general & internal medicine, Framingham Risk Score, Respiration, Area under the curve, Middle Aged, Hospitalization, Survival Rate, Italy, Artificial, Emergency Medicine, Female, Clinical risk factor, 2019-20 coronavirus outbreak, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Ce - Letter to the Editor, MEDLINE, Risk Assessment, 03 medical and health sciences, Predictive Value of Tests, Internal medicine, Internal Medicine, medicine, Intubation, Intratracheal, Humans, In patient, Derivation, COVID-19, Risk prediction model, SARS-CoV 2, Selection (genetic algorithm), Aged, Retrospective Studies, SARS-CoV-2, business.industry, Retrospective cohort study, Respiration, Artificial, Im - Original, Health Care, Intratracheal, ROC Curve, Intubation, business
Abstract: Coronavirus disease of 2019 (COVID-19) is associated with severe acute respiratory failure. Early identification of high-risk COVID-19 patients is crucial. We aimed to derive and validate a simple score for the prediction of severe outcomes. A retrospective cohort study of patients hospitalized for COVID-19 was carried out by the Italian Society of Internal Medicine. Epidemiological, clinical, laboratory, and treatment variables were collected at hospital admission at five hospitals. Three algorithm selection models were used to construct a predictive risk score: backward Selection, Least Absolute Shrinkage and Selection Operator (LASSO), and Random Forest. Severe outcome was defined as the composite of need for non-invasive ventilation, need for orotracheal intubation, or death. A total of 610 patients were included in the analysis, 313 had a severe outcome. The subset for the derivation analysis included 335 patients, the subset for the validation analysis 275 patients. The LASSO selection identified 6 variables (age, history of coronary heart disease, CRP, AST, D-dimer, and neutrophil/lymphocyte ratio) and resulted in the best performing score with an area under the curve of 0.79 in the derivation cohort and 0.80 in the validation cohort. Using a cut-off of 7 out of 13 points, sensitivity was 0.93, specificity 0.34, positive predictive value 0.59, and negative predictive value 0.82. The proposed score can identify patients at low risk for severe outcome who can be safely managed in a low-intensity setting after hospital admission for COVID-19.
Published: 2021

30. High‐mobility group box 1 as a predictive biomarker for drug‐resistant epilepsy: A proof‐of‐concept study

Author: Andrea L. Jorgensen, Lauren Walker, Tiina Alapirtti, Graeme J. Sills, Anthony G Marson, Annamaria Vezzani, Martin J. Brodie, Munir Pirmohamed, and Jukka Peltola
Subjects: Oncology, Drug Resistant Epilepsy, medicine.medical_specialty, chemical and pharmacologic phenomena, Drug resistance, HMGB1, Epilepsy, Seizures, Internal medicine, medicine, Humans, Prospective Studies, HMGB1 Protein, Neuroinflammation, Predictive biomarker, biology, business.industry, medicine.disease, High-mobility group, Neurology, biology.protein, Biomarker (medicine), Neurology (clinical), business, Biomarkers
Abstract: Currently no sensitive and specific biomarkers exist to predict drug-resistant epilepsy. We determined whether blood levels of high-mobility group box 1 (HMGB1), a mediator of neuroinflammation implicated in drug-resistant epilepsies, identifies patients with drug-resistant seizures. Patients with drug-resistant epilepsy express significantly higher levels of blood HMGB1 than those with drug-responsive, well-controlled seizures and healthy controls. No correlation existed between blood HMGB1 levels and total pretreatment seizure count or days since last seizure at new epilepsy diagnosis, indicating that blood HMGB1 does not solely reflect ongoing seizures. HMGB1 distinguishes with high specificity and selectivity drug-resistant versus drug-responsive patients. This protein therefore has potential clinical utility to act as a biomarker for predicting response to therapy, which should be addressed in prospective clinical studies.
Published: 2021

31. Inflammation and reactive oxygen species as disease modifiers in epilepsy

Author: Gaetano Terrone, Teresa Ravizza, Alberto Pauletti, Annamaria Vezzani, Silvia Balosso, Terrone, G, Balosso, S, Pauletti, A, Ravizza, T, and Vezzani, A
Subjects: 0301 basic medicine, Population, Anti-Inflammatory Agents, Disease, medicine.disease_cause, Bioinformatics, Neuroprotection, Epileptogenesis, Antioxidants, 03 medical and health sciences, Cellular and Molecular Neuroscience, Epilepsy, 0302 clinical medicine, Animals, Humans, Medicine, education, Neuroinflammation, Pharmacology, Anakinra, education.field_of_study, business.industry, medicine.disease, Oxidative Stress, 030104 developmental biology, Anticonvulsants, Inflammation Mediators, Reactive Oxygen Species, business, 030217 neurology & neurosurgery, Oxidative stress, medicine.drug
Abstract: Neuroinflammation and reactive oxygen and nitrogen species are rapidly induced in the brain after acute cerebral injuries that are associated with an enhanced risk for epilepsy in humans and related animal models. These phenomena reinforce each others and persist during epileptogenesis as well as during chronic spontaneous seizures. Anti-inflammatory and anti-oxidant drugs transiently administered either before, or shortly after the clinical onset of symptomatic epilepsy, similarly block the progression of spontaneous seizures, and may delay their onset. Moreover, neuroprotection and rescue of cognitive deficits are also observed in the treated animals. Therefore, although these treatments do not prevent epilepsy development, they offer clinically relevant disease-modification effects. These therapeutic effects are mediated by targeting molecular signaling pathways such as the IL-1β-IL-1 receptor type 1 and TLR4, P2X7 receptors, the transcriptional anti-oxidant factor Nrf2, while the therapeutic impact of COX-2 inhibition for reducing spontaneous seizures remains controversial. Some anti-inflammatory and anti-oxidant drugs that are endowed of disease modification effects in preclinical models are already in medical use and have a safety profile, therefore, they provide potential re-purposed treatments for improving the disease course and for reducing seizure burden. Markers of neuroinflammation and oxidative stress can be measured in blood or by neuroimaging, therefore they represent testable prognostic and predictive biomarkers for selecting the patient's population at high risk for developing epilepsy therefore eligible for novel treatments. This article is part of the special issue entitled 'New Epilepsy Therapies for the 21st Century - From Antiseizure Drugs to Prevention, Modification and Cure of Epilepsy'.
Published: 2020

32. Face-from-Depth for Head Pose Estimation on Depth Images

Author: Roberto Vezzani, Matteo Fabbri, Simone Calderara, Rita Cucchiara, Guido Borghi, Guido Borghi, Matteo Fabbri, Roberto Vezzani, Simone Calderara, and Rita Cucchiara
Subjects: FOS: Computer and information sciences, Male, Shoulder, Databases, Factual, Computer science, Computer Vision and Pattern Recognition (cs.CV), Automated Facial Recognition, Posture, Computer Science - Computer Vision and Pattern Recognition, 02 engineering and technology, Convolutional neural network, Pattern Recognition, Automated, Set (abstract data type), Imaging, Three-Dimensional, Artificial Intelligence, Component (UML), 0202 electrical engineering, electronic engineering, information engineering, Humans, Computer vision, Pose, head pose estimation, depth cameras, depth frames, GAN, CNN, business.industry, Applied Mathematics, Frame rate, Computational Theory and Mathematics, Hallucinating, Face (geometry), Face, RGB color model, 020201 artificial intelligence & image processing, Female, Computer Vision and Pattern Recognition, Artificial intelligence, Neural Networks, Computer, business, Head, Software, Algorithms
Abstract: Depth cameras allow to set up reliable solutions for people monitoring and behavior understanding, especially when unstable or poor illumination conditions make unusable common RGB sensors. Therefore, we propose a complete framework for the estimation of the head and shoulder pose based on depth images only. A head detection and localization module is also included, in order to develop a complete end-to-end system. The core element of the framework is a Convolutional Neural Network, called POSEidon+, that receives as input three types of images and provides the 3D angles of the pose as output. Moreover, a Face-from-Depth component based on a Deterministic Conditional GAN model is able to hallucinate a face from the corresponding depth image. We empirically demonstrate that this positively impacts the system performances. We test the proposed framework on two public datasets, namely Biwi Kinect Head Pose and ICT-3DHP, and on Pandora, a new challenging dataset mainly inspired by the automotive setup. Experimental results show that our method overcomes several recent state-of-art works based on both intensity and depth input data, running in real-time at more than 30 frames per second., Comment: Submitted to IEEE Transactions on PAMI, updated version (second round). arXiv admin note: substantial text overlap with arXiv:1611.10195
Published: 2020

33. [Descriptive analytical study on patient mobilization of the Internal Medicine Department of the USL - IRCCS of Reggio Emilia (MOBINT)]

Author: Vezzani, E., Mecugni, D., Silba Cardoso, J., Coriani, S., Boccia Zoboli, A., Ricco, R., Cavuto, S., Savoldi, L., and Amaducci, G.
Subjects: Hospitalization, Internal Medicine, Humans, Prospective Studies, Length of Stay, Aged, Delivery of Health Care
Abstract: Hospitalisation represents a significant risk factor for the decline in the general conditions of the elderly. Loss of autonomy in elderly inpatients, together with immobilisation, has been defined as 'Hospital-Acquired Disability' and affects 65% of this class of patients. Less than half of them will regain independent mobilisation. Included among the negative effects are: falls, increased percentage of admission to nursing homes, longer hospital admissions, increased mortality and morbitity. Despite these facts, elderly patients remain in bed for 83-95% of their hospital stay; they rarely walk or are mobilised. Only on an international level has this issue been analysed OBJECTIVES: To analyse active mobilisation in inpatients.Prospective analytical and descriptive study performed from December 2018 - May 2019 in the Clinical Medicine department of the AUSL of Reggio Emilia. Descriptive analysis of the data has been performed.A total of 1725 patients were screened for the study. After applying the inclusion criteria, 295 patients were enrolled in the study, 9 of which were then excluded for failure to be mobilised. 66.4% of these patients were mobilized the morning during hygiene-rounds. According to the nurse, they appeared in a stable state, alert and oriented (88.1%) and used a variety of aids (from 1 to 3) (57.3%). The frequency of mobilisations were: 44.4% once a day, 31.2% twice, 24.4% three times or more.This study highlighted that mobilisation is strictly correlated to first assistance, frequently relying on health care assistants, and is mostly applied to oriented patients who only need one assistant. Further studies are required to investigate connections between patient's features and mobilisation.L’ospedalizzazione rappresenta un fattore di rischio per il declino delle condizioni generali dell’anziano. La perdita di autonomia dei pazienti anziani ricoverati, associata alla mancata mobilizzazione, è stata definita come una Disabilità Acquisita in Ospedale e colpisce fino al 65% di essi. Meno della metà degli anziani recuperano la mobilizzazione indipendente. Tra gli esiti negativi associati abbiamo: cadute, aumento delle istituzionalizzazioni e dei tempi di degenza, aumentata mortalità, sviluppo di complicanze. Nonostante ciò, gli anziani rimangono allettati per il 83-95% della degenza, solo raramente deambulano o vengono mobilizzati. Solo a livello internazionale è stata indagata questa problematica.Descrivere la mobilizzazione attiva dei pazienti internistici.Studio analitico descrittivo prospettico. Dicembre 2018 - Maggio 2019. Sono stati inclusi i reparti internistici dell’AUSL di Reggio Emilia. È stata eseguita un’analisi descrittiva dei dati.Sono stati screenati 1725 pazienti, applicando i criteri d’inclusione reclutati 295, di cui 9 esclusi perché non mobilizzabili. Il 66,4% dei pazienti viene mobilizzato al mattino durante l’igiene. Essi sono in condizioni stabili secondo l’infermiere, lucidi ed orientati (88,1%) e portatori di vari presidi (da 1 a 3) (57,3%). La frequenza di mobilizzazione è di: una volta al giorno per il 44,4% dei pazienti, due volte al giorno per il 31,2% e più di due volte al giorno per il 24,4%.Lo studio ha evidenziato che la mobilizzazione è strettamente associata all’assistenza di base, nella quale ha un ruolo rilevante l’OSS. Essa riguarda prevalentemente pazienti lucidi orientati e che richiedono un solo operatore. Sarebbero auspicabili studi successivi per indagare correlazioni fra caratteristiche dei pazienti e mobilizzazione.
Published: 2021

34. Testosterone positively regulates vagina NO-induced relaxation: an experimental study in rats

Author: I, Cellai, S, Filippi, P, Comeglio, S, Cipriani, E, Maseroli, V, Di Stasi, T, Todisco, S, Marchiani, L, Tamburrino, F, Villanelli, S, Vezzani, C, Corno, M, Fambrini, G, Guarnieri, E, Sarchielli, A, Morelli, G, Rastrelli, M, Maggi, and L, Vignozzi
Subjects: Rats, Sprague-Dawley, Estradiol, Ovariectomy, Letrozole, Vagina, Animals, Humans, RNA, Female, Testosterone, Nitric Oxide, Acetylcholine, Rats
Abstract: Female sexual response involves a complex interplay between neurophysiological mechanisms and the nitric oxide (NO)-mediated relaxation of clitoris and vagina. The aim of this study was to evaluate sex steroids regulation of the relaxant pathway in vagina, using a validated animal model.Subgroups of OVX Sprague-Dawley rats were treated with 17β-estradiol, testosterone, or testosterone and letrozole, and compared with a group of intact animals. Masson's trichrome staining was performed for morphological evaluation of the distal vaginal wall, in vitro contractility studies investigated the effect of OVX and in vivo treatments on vaginal smooth muscle activity. RNA from vaginal tissue was analyzed by semi-quantitative RT-PCR.Immunohistochemical analysis showed that OVX induced epithelial and smooth muscle structural atrophy, testosterone and testo + letrozole increased the muscle bundles content and organization without affecting the epithelium while 17β-estradiol mediated the opposite effects. In vitro contractility studies were performed on noradrenaline pre-contracted vaginal strips from each experimental group. Acetylcholine (0.001-10 µM) stimulation induced a concentration-dependent relaxation, significantly reduced by NO-synthase inhibitor L-NAME and by guanylate cyclase inhibitor ODQ. OVX resulted in a decreased responsiveness to acetylcholine, restored by testosterone, with or without letrozole, but not by 17β-estradiol. OVX sensitivity to the NO-donor SNP was higher than in the control. Vardenafil, a PDE5 inhibitor, enhanced SNP effect in OVX + testosterone as well as in control, as supported by RNA expression analysis.Our study demonstrates that testosterone improves the NO-mediated smooth muscle vaginal cells relaxation confirming its role in maintaining the integrity of muscular relaxant machinery.
Published: 2021

35. Microglia proliferation plays distinct roles in acquired epilepsy depending on disease stages

Author: Milica Cerovic, Diletta Sorrentino, Teresa Ravizza, Nicola Marchi, Marco Bacigaluppi, Rossella Di Sapia, Valentina Kebede, Giorgia Serena Gullotta, Etienne Audinat, Annamaria Vezzani, Martina Di Nunzio, IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri' [Milan, Italy], Hospital San Raffaele & University Vita-Salute Milano, Institut de Génomique Fonctionnelle (IGF), and Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, Kainic acid, [SDV]Life Sciences [q-bio], Hippocampus, Status epilepticus, Neuroprotection, Epileptogenesis, 03 medical and health sciences, Epilepsy, chemistry.chemical_compound, Mice, 0302 clinical medicine, Status Epilepticus, Seizures, Internal medicine, medicine, Animals, Humans, Cell Proliferation, Kainic Acid, Microglia, business.industry, medicine.disease, CSF1 receptor, microglia proliferation, 3. Good health, Barnes maze, Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, Neurology, chemistry, nervous system, epileptogenesis, neuroprotection, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: International audience; Objective: Microgliosis occurs in animal models of acquired epilepsy and in patients. It includes cell proliferation that is associated with seizure frequency and decreased neuronal cells in human epilepsy. The role of microglia proliferation in the development of acquired epilepsy is unknown; thus, we examined its contribution to spontaneous seizure, neurodegeneration, and cognitive deficits in different disease phases.Methods: We used a model of acquired epilepsy triggered by intra-amygdala kainic acid in C57BL6N adult male mice. Mice were electroencephalographically (EEG) monitored (24/7) during status epilepticus and in early and chronic disease. Microglia proliferation was blocked by GW2580, a selective CSF1 receptor inhibitor, supplemented in the diet for 21 days from status epilepticus onset. Then, mice were returned to placebo diet until experiment completion. Control mice were exposed to status epilepticus and fed with placebo diet. Experimental mice were tested in the novel object recognition test (NORT) and in Barnes maze, and compared to control and sham mice. At the end of the behavioral test, mice were killed for brain histopathological analysis. Additionally, seizure baseline was monitored in chronic epileptic mice, then mice were fed for 14 days with GW2580 or placebo diet under 24/7 EEG recording.Results: GW2580 prevented microglia proliferation in mice undergoing epilepsy, whereas it did not affect microglia or basal excitatory neurotransmission in the hippocampus of naive mice. Mice with occluded microglia proliferation during early disease development underwent status epilepticus and subsequent epilepsy similar to placebo diet mice, and were similarly impaired in NORT, with improvement in Barnes maze. GW2580-treated mice displayed neuroprotection in the hippocampus. In contrast, blockade of microglia proliferation in chronic epileptic mice resulted in spontaneous seizure reduction versus placebo mice.Significance: Microglia proliferation during early disease contributes to neurodegeneration, whereas in late chronic disease it contributes to seizures. Timely pharmacological interference with microglia proliferation may offer a potential target for improving disease outcomes.
Published: 2021

36. Large intrathyroidal lipoma with radioiodine uptake

Author: Cecilia Botti, Silvia Vezzani, Simonetta Piana, Andrea Frasoldati, and Angelo Ghidini
Subjects: medicine.medical_specialty, Radioiodine uptake, business.industry, Endocrinology, Diabetes and Metabolism, Biological Transport, Lipoma, medicine.disease, Graves Disease, Iodine Radioisotopes, Endocrinology, medicine, Humans, Radiology, business
Published: 2020

37. Neuroinflammatory pathways as treatment targets and biomarkers in epilepsy

Author: Teresa Ravizza, Silvia Balosso, and Annamaria Vezzani
Subjects: 0301 basic medicine, Disease, Bioinformatics, 03 medical and health sciences, Cellular and Molecular Neuroscience, Epilepsy, 0302 clinical medicine, Treatment targets, Transforming Growth Factor beta, Animals, Humans, Medicine, Neuroinflammation, Predictive biomarker, Arachidonic Acid, business.industry, Receptors, Interleukin-1, Pharmacoresistant epilepsy, medicine.disease, Cell loss, Toll-Like Receptor 4, Oxidative Stress, 030104 developmental biology, Prostaglandins, Molecular targets, Encephalitis, Neurology (clinical), business, Biomarkers, 030217 neurology & neurosurgery, Signal Transduction
Abstract: Epilepsy is a chronic neurological disease characterized by an enduring propensity for generation of seizures. The pathogenic processes of seizure generation and recurrence are the subject of intensive preclinical and clinical investigations as their identification would enable development of novel treatments that prevent epileptic seizures and reduce seizure burden. Such treatments are particularly needed for pharmacoresistant epilepsies, which affect ~30% of patients. Neuroinflammation is commonly activated in epileptogenic brain regions in humans and is clearly involved in animal models of epilepsy. An increased understanding of neuroinflammatory mechanisms in epilepsy has identified cellular and molecular targets for new mechanistic therapies or existing anti-inflammatory drugs that could overcome the limitations of current medications, which provide only symptomatic control of seizures. Moreover, inflammatory mediators in the blood and molecular imaging of neuroinflammation could provide diagnostic, prognostic and predictive biomarkers for epilepsy, which will be instrumental for patient stratification in future clinical studies. In this Review, we focus on our understanding of the IL-1 receptor-Toll-like receptor 4 axis, the arachidonic acid-prostaglandin cascade, oxidative stress and transforming growth factor-β signalling associated with blood-brain barrier dysfunction, all of which are pathways that are activated in pharmacoresistant epilepsy in humans and that can be modulated in animal models to produce therapeutic effects on seizures, neuronal cell loss and neurological comorbidities.
Published: 2019

38. The mediating role of emotions in the relation between beliefs and teachers' job satisfaction

Author: Giulia Vettori, Lucia Bigozzi, Claudio Vezzani, and Giuliana Pinto
Subjects: Arts and Humanities (miscellaneous), Emotions, Developmental and Educational Psychology, Humans, Experimental and Cognitive Psychology, General Medicine, School Teachers, Job Satisfaction
Abstract: This study investigates the patterns of relations between beliefs, emotions, and job satisfaction in 249 Italian in-service teachers. Participants were assessed on their growth and fixed mindsets, self-efficacy beliefs, emotions associated with various components of their professional engagement and job satisfaction. Mediational analyses shed light on the mediating role of teaching and role emotions in the relation between beliefs and job satisfaction. Specifically, teachers' high self-efficacy beliefs positively impact on job satisfaction if negative teaching and role emotions are contained at low levels.
Published: 2021

39. Strategies to Tackle Antimicrobial Resistance: The Example of Escherichia coli and Pseudomonas aeruginosa

Author: Rossella Cuffaro, Sonia Nicchi, Serena Tondi, Isabel Delany, Paolo Cinelli, Benedetta Manca, Giacomo Vezzani, Giada Antonelli, Viola Viviani, Maria Scarselli, Luigia Cappelli, and Francesca Schiavetti
Subjects: 0301 basic medicine, medicine.drug_class, QH301-705.5, 030106 microbiology, Antibiotics, Context (language use), Review, medicine.disease_cause, Catalysis, Microbiology, Inorganic Chemistry, 03 medical and health sciences, Antibiotic resistance, Immune system, Antigen, antimicrobial resistance (AMR), vaccine, Drug Resistance, Bacterial, Escherichia coli, medicine, Animals, Humans, Pseudomonas Infections, Physical and Theoretical Chemistry, Biology (General), Molecular Biology, QD1-999, Escherichia coli Infections, Spectroscopy, outer membrane vesicles (OMV), biology, Pseudomonas aeruginosa, Organic Chemistry, antigen identification, General Medicine, Antimicrobial, biology.organism_classification, Computer Science Applications, monoclonal antibodies (mAbs), Chemistry, 030104 developmental biology, Bacterial Vaccines, Bacteria
Abstract: Traditional antimicrobial treatments consist of drugs which target different essential functions in pathogens. Nevertheless, bacteria continue to evolve new mechanisms to evade this drug-mediated killing with surprising speed on the deployment of each new drug and antibiotic worldwide, a phenomenon called antimicrobial resistance (AMR). Nowadays, AMR represents a critical health threat, for which new medical interventions are urgently needed. By 2050, it is estimated that the leading cause of death will be through untreatable AMR pathogens. Although antibiotics remain a first-line treatment, non-antibiotic therapies such as prophylactic vaccines and therapeutic monoclonal antibodies (mAbs) are increasingly interesting alternatives to limit the spread of such antibiotic resistant microorganisms. For the discovery of new vaccines and mAbs, the search for effective antigens that are able to raise protective immune responses is a challenging undertaking. In this context, outer membrane vesicles (OMV) represent a promising approach, as they recapitulate the complete antigen repertoire that occurs on the surface of Gram-negative bacteria. In this review, we present Escherichia coli and Pseudomonas aeruginosa as specific examples of key AMR threats caused by Gram-negative bacteria and we discuss the current status of mAbs and vaccine approaches under development as well as how knowledge on OMV could benefit antigen discovery strategies.
Published: 2021

40. The association between systemic autoimmune disorders and epilepsy and its clinical implications

Author: Roland D. Thijs, Maarten J. Titulaer, Claude Steriade, Josemir W. Sander, and Annamaria Vezzani
Subjects: 0301 basic medicine, Population, Comorbidity, medicine.disease_cause, comorbidities, Autoimmunity, Autoimmune Diseases, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Immune system, SDG 3 - Good Health and Well-being, medicine, Humans, education, seizures, Autoimmune encephalitis, education.field_of_study, Type 1 diabetes, business.industry, autoimmunity, Symptomatic seizures, medicine.disease, Acquired immune system, acute symptomatic seizures, 030104 developmental biology, Immunology, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Systemic autoimmune disorders occur more frequently in patients with epilepsy than in the general population, suggesting shared disease mechanisms. The risk of epilepsy is elevated across the spectrum of systemic autoimmune disorders but is highest in systemic lupus erythematosus and type 1 diabetes mellitus. Vascular and metabolic factors are the most important mediators between systemic autoimmune disorders and epilepsy. Systemic immune dysfunction can also affect neuronal excitability, not only through innate immune activation and blood–brain barrier dysfunction in most epilepsies but also adaptive immunity in autoimmune encephalitis. The presence of systemic autoimmune disorders in subjects with acute seizures warrants evaluation for infectious, vascular, toxic and metabolic causes of acute symptomatic seizures, but clinical signs of autoimmune encephalitis should not be missed. Immunosuppressive medications may have antiseizure properties and trigger certain drug interactions with antiseizure treatments. A better understanding of mechanisms underlying the co-existence of epilepsy and systemic autoimmune disorders is needed to guide new antiseizure and anti-epileptogenic treatments. This review aims to summarize the epidemiological evidence for systemic autoimmune disorders as comorbidities of epilepsy, explore potential immune and non-immune mechanisms, and provide practical implications on diagnostic and therapeutic approach to epilepsy in those with comorbid systemic autoimmune disorders.
Published: 2021

41. Characteristics of a nationwide cohort of patients presenting with isolated hypogonadotropic hypogonadism (IHH)

Author: Marco Bonomi, Valeria Vezzoli, Csilla Krausz, Fabiana Guizzardi, Silvia Vezzani, Manuela Simoni, Ivan Bassi, Paolo Duminuco, Natascia Di Iorgi, Claudia Giavoli, Alessandro Pizzocaro, Gianni Russo, Mirella Moro, Letizia Fatti, Alberto Ferlin, Laura Mazzanti, Maria Chiara Zatelli, Salvo Cannavò, Andrea M Isidori, Angela Ida Pincelli, Flavia Prodam, Antonio Mancini, Paolo Limone, Maria Laura Tanda, Rossella Gaudino, Mariacarolina Salerno, Pregnolato Francesca, Mohamad Maghnie, Mario Maggi, Luca Persani, G Aimaretti, M Altobelli, M R Ambrosio, M Andrioli, G Angeletti, F Arecco, G Arnaldi, M Arosio, A Balsamo, M Baldassarri, L Bartalena, N Bazzoni, L Beccaria, P Beck-Peccoz, G Bellastella, M Bellizzi, F Benedicenti, S Bernasconi, C Bizzarri, G Bona, S Bonadonna, G Borretta, M Boschetti, A Brunani, V Brunelli, F Buzi, C Cacciatore, B Cangiano, M Cappa, R Casalone, A Cassio, P Cavarzere, V Cherubini, T Ciampani, D Cicognani, A Cignarelli, M Cisternino, P Colombo, S Corbetta, N Corciulo, G Corona, R Cozzi, C Crivellaro, I Dalle Mule, L Danesi, A V D’Elia, E degli Uberti, S De Leo, E Della Valle, M De Marchi, N Di Iorgi, A Di Mambro, A Fabbri, C Foresta, G Forti, A R Franceschi, A Garolla, M Ghezzi, C Giacomozzi, M Giusti, E Grosso, G Guabello, M P Guarneri, G Grugni, A M Isidori, F Lanfranco, A Lania, R Lanzi, L Larizza, A Lenzi, S Loche, P Loli, V Lombardi, M C Maggio, G Mandrile, C Manieri, G Mantovani, S Marelli, M Marzullo, M A Mencarelli, N Migone, G Motta, G Neri, G Padova, G Parenti, B Pasquino, A Pia, E Piantanida, E Pignatti, A Pilotta, B Pivetta, M Pollazzon, A Pontecorvi, P Porcelli, G B Pozzan, G Pozzobon, G Radetti, P Razzore, L Rocchetti, R Roncoroni, G Rossi, E Sala, A Salvatoni, F Salvini, A Secco, M Segni, R Selice, P Sgaramella, F Sileo, A A Sinisi, F Sirchia, A Spada, A Tresoldi, R Vigneri, G Weber, S Zucchini, Bonomi, Marco, Vezzoli, Valeria, Krausz, Csilla, Guizzardi, Fabiana, Vezzani, Silvia, Simoni, Manuela, Bassi, Ivan, Duminuco, Paolo, Di Iorgi, Natascia, Giavoli, Claudia, Pizzocaro, Alessandro, Russo, Gianni, Moro, Mirella, Fatti, Letizia, Ferlin, Alberto, Mazzanti, Laura, Zatelli Maria, Chiara, Cannavò, Salvo, Isidori Andrea, M., Pincelli Angela, Ida, Prodam, Flavia, Mancini, Antonio, Limone, Paolo, Tanda Maria, Laura, Gaudino, Rossella, Salerno, Mariacarolina, Francesca, Pregnolato, Maghnie, Mohamad, Maggi, Mario, Persani, Luca, Italian Network on Central, Hypogonadism., Zatelli, Maria Chiara, Cannavã², Salvo, Isidori, Andrea M., Pincelli, Angela Ida, Tanda, Maria Laura, Aimaretti, G., Altobell, M., Ambrosio, M. R., Andrioli, M., Angelett, G., Arecco, F., Arnald, G., Arosio, M., Balsamo, A., Baldassarr, M., Bartalena, L., Bazzon, N., Beccari, L., Beck-Peccoz, P., Bellastella, G., Bellizz, M., Benedicent, F., Bernasconi, S., Bizzarri, C., Bona, G., Bonadonna, S., Borrett, G., Boschetti, M., Brunani, A., Brunelli, V., Buz, F., Cacciatore, C., Cangiano, B., Cappa, M., Casalone, R., Cassio, A., Cavarzere, P., Cherubini, V., Ciampani, T., Cicognan, D., Cignarell, A., Cisternin, M., Colombo, P., Corbetta, S., Corciul, N., Corona, G., Cozzi, R., Crivellaro, C., Dalle Mule, I., Danesi, L., Eli, A. V. D., Degli Uberti, E., De Leo, S., Della Valle, E., De Marchi, M., Di Iorgi, N., Di Mambr, A., Fabbri, A., Foresta, C., Forti, G., Franceschi, A. R., Garolla, A., Ghezzi, M., Giacomozzi, C., Giusti, M., Grosso, E., Guabello, G., Guarneri, M. P., Grugni, G., Isidori, A. M., Lanfranco, F., Lania, A., Lanzi, R., Larizza, L., Lenzi, A., Loche, S., Loli, P., Lombardi, V., Maggi, M. C., Mandrile, G., Manieri, C., Mantovani, G., Marelli, S., Marzullo, M., Mencarelli, M. A., Migone, N., Motta, G., Neri, G., Padov, G., Parenti, G., Pasquino, B., Pia, A., Piantanida, E., Pignatti, E., Pilotta, A., Pivett, B., Pollazzon, M., Pontecorvi, A., Porcelli, P., Pozza, G. B., Pozzobon, G., Radetti, G., Razzore, P., Rocchett, L., Roncoron, R., Rossi, G., Sala, E., Salvatoni, A., Salvini, F., Secc, A., Segni, M., Selice, R., Sgaramella, P., Sileo, F., Sinisi, A. A., Sirchia, F., Spada, A., Tresoldi, A., Vigneri, R., Weber, G., Zucchini, S., Marco Bonomi, Valeria Vezzoli, Csilla Krausz, Fabiana Guizzardi, Silvia Vezzani, Manuela Simoni, Ivan Bassi, Paolo Duminuco, Natascia Di Iorgi, Claudia Giavoli, Alessandro Pizzocaro, Gianni Russo, Mirella Moro, Letizia Fatti, Alberto Ferlin, Laura Mazzanti, Maria Chiara Zatelli, Salvo Cannavò, Andrea M Isidori, Angela Ida Pincelli, Flavia Prodam, Antonio Mancini, Paolo Limone, Maria Laura Tanda, Rossella Gaudino, Mariacarolina Salerno, Pregnolato Francesca, Mohamad Maghnie, Mario Maggi, Luca Persani, Italian Network on Central Hypogonadism […, A. Cassio, …, S. Zucchini, ], Isidori, Andrea M, Weber, Giovanna, and Italian Network on Central, Hypogonadism
Subjects: 0301 basic medicine, Male, Pediatrics, Synkinesis, Kallmann syndrome, diagnosis, genotype, Endocrinology, Diabetes and Metabolism, Gonadal Steroid Hormone, Cohort Studies, Olfaction Disorders, 0302 clinical medicine, Endocrinology, Olfaction Disorder, Young adult, Age of Onset, Gonadal Steroid Hormones, Gonadotropin, Pituitary Hormone, Isolated hypogonadotropic hypogonadism, General Medicine, isolated hypogonadotropic hypogonadism, pubertal delay, genetic-basis, gonadotropin-deficiency, Diabetes and Metabolism, Phenotype, Italy, Cohort, Female, complex, Cohort study, Human, Adult, medicine.medical_specialty, Adolescent, Gonadotropins, Humans, Hypogonadism, Obesity, Overweight, Pituitary Hormones, Young Adult, 030209 endocrinology & metabolism, NO, 03 medical and health sciences, Hypogonadotropic hypogonadism, Adolescent, Adult, Age of Onset, Cohort Studies, Female, Gonadal Steroid Hormones, Gonadotropins, Humans, Hypogonadis, Italy, Male, Obesity, Olfaction Disorders, Overweight, Phenotype, Pituitary Hormones, Synkinesis, Young Adult, Endocrinology, Diabetes and Metabolism, Endocrinology, Internal medicine, medicine, Isolated hypogonadotropic hypogonadism, Kallmann syndrome, Observational cohort study, gnrh deficiency, disease, business.industry, Settore MED/13 - ENDOCRINOLOGIA, isolated Hypogonadotropic hypogonadism, kallmann syndrome, medicine.disease, body regions, 030104 developmental biology, Sex steroid, linked kallmann-syndrome, heterogeneity, phenotype, Observational cohort study, Synkinesi, Age of onset, Cohort Studie, business
Abstract: Objective Isolated hypogonadotropic hypogonadism (IHH) is a rare disorder with pubertal delay, normal (normoosmic-IHH, nIHH) or defective sense of smell (Kallmann syndrome, KS). Other reproductive and non-reproductive anomalies might be present although information on their frequency are scanty, particularly according to the age of presentation. Design Observational cohort study carried out between January 2008 and June 2016 within a national network of academic or general hospitals. Methods We performed a detailed phenotyping of 503 IHH patients with: (1) manifestations of hypogonadism with low sex steroid hormone and low/normal gonadotropins; (2) absence of expansive hypothalamic/pituitary lesions or multiple pituitary hormone defects. Cohort was divided on IHH onset (PPO, pre-pubertal onset or AO, adult onset) and olfactory function: PPO-nIHH (n = 275), KS (n = 184), AO-nIHH (n = 36) and AO-doIHH (AO-IHH with defective olfaction, n = 8). Results 90% of patients were classified as PPO and 10% as AO. Typical midline and olfactory defects, bimanual synkinesis and familiarity for pubertal delay were also found among the AO-IHH. Mean age at diagnosis was significantly earlier and more frequently associated with congenital hypogonadism stigmata in patients with Kallmann’s syndrome (KS). Synkinesis, renal and male genital tract anomalies were enriched in KS. Overweight/obesity are significantly associated with AO-IHH rather than PPO-IHH. Conclusions Patients with KS are more prone to develop a severe and complex phenotype than nIHH. The presence of typical extra-gonadal defects and familiarity for PPO-IHH among the AO-IHH patients indicates a common predisposition with variable clinical expression. Overall, these findings improve the understanding of IHH and may have a positive impact on the management of patients and their families.
Published: 2018

42. Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018): Change management in allergic rhinitis and asthma multimorbidity using mobile technology

Author: Karin C. Lødrup Carlsen, L. Cecchi, F. Portejoie, T. Vontetsianos, Olivier Vandenplas, M. van Hague, D. Mora Bogado, M. Illario, Dana Wallace, L. Namazova-Baranova, E. Asayag, I. Ribeirinho, E. Costa, Shona Pedersen, Inger Kull, Davor Plavec, M. Morais-Almeida, Mickael Bewick, N.H. Chavannes, I. J. Ansotegui, G. De Carlo, K. S. Bennoor, Faradiba Sarquis Serpa, S. Arnavielle, F. Corti, Moises A. Calderon, Martín Bedolla-Barajas, Mette Sørensen, Isabella Annesi-Maesano, Elaine Colgan, Przemyslaw Kardas, M. van Eerd, Jorge Maspero, Valérie Siroux, Isabelle Momas, Ralph Mösges, Yves Dauvilliers, T. Keil, T. Bieber, Marit Westman, Rachel Nadif, O. Pfaar, A.C. Carvalho Coehlo, R. M. Cortés-Grimaldo, I. Skrindo, Piotr Kuna, Nicola Scichilone, Antonella Muraro, Kimihiro Okubo, Paulo Augusto Moreira Camargos, C. Cartier, Oliver Pfaar, K. Ohta, Barbara P. Yawn, Igor Kaidashev, Michel Thibaudon, X. Basagana, I. Kaidashev, Bilun Gemicioglu, S. Genova, Hae-Sim Park, J.J. Matta Campos, Simon Walker, Ulf Darsow, Fulvio Braido, J. Salimäki, T. Zuberbier, Raphaël Chiron, Mohammad Reza Masjedi, G.D. Marshall, Branislava Milenkovic, W. J. Fokkens, Eric D. Bateman, Robert M. Naclerio, Steve Montefort, M. de Fátima Emerson, T. Werfel, Cemal Cingi, A. Szylling, Martin Wagenmann, I. Baiardini, L. T. T. Le, N. Khaltaev, Ki-Suck Jung, Agnieszka Lipiec, Panayiotis K. Yiallouros, A Valero, R. Gerth van Wijk, L. Hernández, Marek L. Kowalski, C. Zubrinich, Sinthia Bosnic-Anticevich, Miguel A. Sierra, Erik Melén, T. Haahtela, Rute Almeida, Violeta Kvedariene, R. Pawankar, T.A. Popov, Flore Amat, Sanna Toppila-Salmi, M. Gotua, A. Sheikh, A. Bedbrook, Torsten Zuberbier, B. De Martino, Gérard Dray, Francesca Avolio, E. Mandajieva, B. Samolinski, Petr Panzner, P. Kuna, Philippe-Jean Bousquet, T. D. Nyembue, Luo Zhang, Leyla Namazova-Baranova, Ana Maria Carriazo, João Fonseca, E. Van Ganse, Roland Buhl, M. Bochenska Marciniak, Cristiana Stellato, J. da Silva, J. E. Gereda, Han-Jung Park, M.C. Costa-Dominguez, W. Carr, Dirceu Solé, S. Forti, Nanshan Zhong, Jordi Sunyer, Alain Didier, Y. Z. Chen, Thomas B. Casale, Jim Phillips, Isabelle Bosse, Manuel Teixeira Veríssimo, D. Y. Wang, U. Trama, Cristina Bárbara, David Somekh, T. Camuzat, R. N. Naclerio, Enrico Novellino, Leszek Klimek, M. Rodriguez Gonzalez, Holger J. Schünemann, Mario Barbagallo, D. Larenas-Linnemann, Mario Sánchez-Borges, Massimo Triggiani, Y. Okamoto, E. Mathieu-Dupas, N. Di Carluccio, S. Toppila-Salmi, Omer Kalayci, Rudolf Valenta, J. Coll, F. de Blay, Wienczyslawa Czarlewski, W. Pohl, Piotr Wroczyński, Kian Fan Chung, Nikolaos G. Papadopoulos, Pascal Demoly, Hubert Blain, M. Crescenzo, O. Kalayci, Leocadio Rodríguez-Mañas, G. Moda, L. Cox, Z. Gutter, A. Mair, Andrew Bush, Maria-Dolores Mogica-Martinez, Giorgio Walter Canonica, Antonio Valero, Daniel Laune, A. Zurkuhlen, Paul C. Potter, D. Wallace, Gabrielle L. Onorato, Mihaela Zidarn, E.P. Prokopakis, Anne Lise Courbis, Sergio Bonini, Ruta Dubakiene, A. Papi, Y. El-Gamal, Jacques Mercier, Wytske Fokkens, Rodolphe Bourret, S. Palkonen, A. Yorgancioglu, G. Vezzani, J. A. Rizzo, D. Plavec, D. Caillot, G. De Feo, E. Menditto, Caterina Bucca, A. C. Pozzi, Hironori Sagara, I. Grisle, I. Pin, Christopher E. Brightling, Ludger Klimek, F.F. Morato-Castro, Désirée Larenas-Linnemann, Alessandro Vatrella, A. A. Cruz, Guy Joos, E.D. Bateman, Erendira Rodriguez-Zagal, H. Douagui, T. To, Edgardo Jares, C. Bindslev-Jensen, G. Levato, J. O. B. Hourihane, R. Rajabian-Soderlund, C. Odzhakova, J. Bousquet, M. T. Ventura, Arzu Yorgancioglu, Osman M. Yusuf, H. J. Zar, Giovanni Rolla, Sebastian L. Johnston, M.S. Dykewicz, Esben Eller, A. Gamkrelidze, Filip Raciborski, Renzo Angles, Rafael Stelmach, M. Nogues, David Price, Mário Morais-Almeida, Tari Haahtela, Teresa To, D. Conforti, Stephen R. Durham, S. Gonzalez Diaz, V. Cardona, Werner Aberer, B. Milenkovic, Luigi Napoli, K. C. Bergmann, P W Hellings, M. Lessa, P. Panzner, Alfonso M. Cepeda Sarabia, M. Guidacci, A.L. Matos, Todor A. Popov, C. Suppli Ulrik, Diana Deleanu, N. de Paula Motta Rubini, Carsten Bindslev-Jensen, I. Majer, Ioana Agache, B. A. Barreto, R. Picard, Erkka Valovirta, A. Fink-Wagner, L. Colas, João O. Malva, Thomas Keil, M. T. Burguete Cabañas, Bolesław Samoliński, M.H. Garcia-Cruz, L.P. Boulet, K. Nekam, Edyta Krzych-Fałta, P. Devillier, J. Ferreira de Mello, Jussi Karjalainen, I. Bogus-Buczynska, Susan Waserman, Marcus Maurer, Tomas Chivato, Elena Bacci, M. Przemecka, Olga Lourenço, José Miguel Fuentes-Pérez, M. Zidarn, Talant Sooronbaev, J.M. Anto, W. Czarlewski, R. Murray, Luís Nogueira-Silva, G. Passalacqua, E. Chkhartishvili, Oscar Mayora, Victoria Cardona, M. Sondermann, Piotr Lacwik, S. Ouedraogo, I. Baroni, Artur Z. Białoszewski, G Scadding, J. Strozek, R. Emuzyte, Neven Miculinic, Ruby Pawankar, Ken Ohta, I. Agache, J.L. Gálvez-Romero, Nikos G. Papadopoulos, E. O. Meltzer, I. Annesi-Maesano, E. De Manuel Keenoy, Jorge A. Luna-Pech, Ana Margarida Pereira, Paul Potter, M. Ortega Cisneros, J. Li, K. F. Rabe, M. Rottem, Mikael Benson, Ali Fuat Kalyoncu, Dermot Ryan, Dieter Maier, C.Y. García-Cobas, S. Bialek, G. Du Toit, S. Shamai, S. Mavale-Manuel, Rojin Rajabian-Soderlund, Maddalena Illario, Philippe Devillier, F. Rodenas, Emmanuel P. Prokopakis, De Yun Wang, Niels H. Chavannes, E.H.D. Bel, Bianca Beghe, Sietze Reitsma, John Wright, O. Lourenço, L.T.T. Le, Josep M. Antó, T. Casale, Paul K. Keith, K. C. Lødrup Carlsen, P. Demoly, Mikael Kuitunen, Marc Humbert, A. M. Cepeda Sarabia, Ignacio J. Ansotegui, M.C. Rizzo, Davide Caimmi, Milan Sova, Nick A. Guldemond, P. Yakovliev, Judah A. Denburg, Jaime Correia de Sousa, Elisabete Melo-Gomes, Aziz Sheikh, I. Bosse, M. M. Ciaravolo, S. Di Capua Ercolano, Alpana Mair, P. Lieberman, Isabella Pali-Schöll, Leif Bjermer, G. De Vries, M. Roman Rodriguez, Johanna Salimäki, Carmen Panaitescu, F. Mihaltan, Giulia De Feo, F. E. R. Simons, A. Blua, B. Mahboub, D. Ryan, M. Bewick, Anabela Mota-Pinto, J.A. Fonseca, Neil Wilson, Marek Jutel, Dennis M. Williams, M. Akdis, Menachem Rottem, Marcello Persico, J. C. Ivancevich, Nelson Rosario, A. Farsi, Alvaro A. Cruz, Liguo Zhang, Anna Bedbrook, L. Bertorello, Magnus Wickman, Marilyn Urrutia-Pereira, O. Spranger, René Maximiliano Gómez, C. Bachert, Renaud Louis, Musa Khaitov, C. Stellato, Constantinos Pitsios, Roland Buonaiuto, A. Romano, Sîan A Williams, R. Puy, Daniela Rivero-Yeverino, Y. Mohammad, J. Farrell, Jan Brozek, Ricardo Pio Monti, E. Paulino, J. Correia de Sousa, Miguel Alejandro Medina-Ávalos, Jocelyne Just, Peter Valentin Tomazic, Jean-François Ferrero, Antoine Magnan, S. Waserman, J Rosado-Pinto, Maciek Kupczyk, C.S. Bosnic-Anticevich, T. Dedeu, Tommi Vasankari, R. Mösges, Robin O'Hehir, Ema Paulino, Peter Hellings, A. Neou, M. Wickman, D. Lauri, Jean Bousquet, A. Ciceran, Jacques Bouchard, Yehia El-Gamal, M.G. Dominguez-Silva, M.R. Alberti, Jean-Louis Pépin, Kimi Okubo, Juan Carlos Ivancevich, Patrik Eklund, Benoit Pugin, C. Dario, Mussa Khaitov, Luisa Brussino, A.G. Chuchalin, Elísio Costa, Susanna Palkonen, Lars Münter, Pedro Carreiro-Martins, R.E. Pulido Ross, Ettore Novellino, Kai-Håkon Carlsen, María Antonieta Guzmán, G.W. Canonica, Gabriel Onorato, Giuseppe De Carlo, R.E. Roller-Wirnsberger, Brian J. Lipworth, M. A. Guzman, J.N. Tebyriçá, Adnan Custovic, Yoshitaka Okamoto, Rimantas Stukas, P. Manning, J. Sastre-Dominguez, Caroline L.S. George, Robyn E O'Hehir, K. Maciej, Bassam Mahboub, J. F. Fontaine, Arũnas Valiulis, Xavier Rodó, D. Vicheva, G. Canfora, Vitalis Briedis, S. Rodrigues Valle, Mark S. Dykewicz, Joanne Rimmer, G. Castellano, B. Pigearias, A. L. Boner, Yunuen Rocío Huerta-Villalobos, Christine Rolland, H. Neffen, H. Arshad, Javier Gómez-Vera, P. Moura Santo, Frederic Viart, F. Blasi, J. Garcia-Aymerich, Lorenzo Cecchi, V. Niedeberger, Giorgio Ciprandi, F. Caballero-Fonseca, Jean-François Fontaine, J Mullol, Maurizio Romano, M. Viegi, Mario E. Zernotti, Arunas Valiulis, Anna Asarnoj, Antonio Nieto, J. Lavrut, D. Dokic, V. Kvedariene, Ewa Jassem, Cezmi A. Akdis, Ruth Murray, Claus Bachert, Peter Schmid-Grendelmeier, Emilie Burte, Joaquim Mullol, Guido Iaccarino, J. Kleine-Tebbe, P. V. Tomazic, E. Eller, Alessandro Fiocchi, H.J. Schunemann, M. Sorlini, C. Robalo-Cordeiro, Ana-Maria Todo-Bom, J. Brozek, Marco Nalin, Matteo Bonini, J. C. Sisul, S.E. Dahlen, F. Amat, Juan Carlos Sisul, Jawad Hajjam, Ana Todo-Bom, Enrica Menditto, Bousquet J., Hellings P.W., Agache I., Amat F., Annesi-Maesano I., Ansotegui I.J., Anto J.M., Bachert C., Bateman E.D., Bedbrook A., Bennoor K., Bewick M., Bindslev-Jensen C., Bosnic-Anticevich S., Bosse I., Brozek J., Brussino L., Canonica G.W., Cardona V., Casale T., Cepeda Sarabia A.M., Chavannes N.H., Cecchi L., Correia de Sousa J., Costa E., Cruz A.A., Czarlewski W., De Carlo G., De Feo G., Demoly P., Devillier P., Dykewicz M.S., El-Gamal Y., Eller E.E., Fonseca J.A., Fontaine J.-F., Fokkens W.J., Guzman M.-A., Haahtela T., Illario M., Ivancevich J.-C., Just J., Kaidashev I., Khaitov M., Kalayci O., Keil T., Klimek L., Kowalski M.L., Kuna P., Kvedariene V., Larenas-Linnemann D., Laune D., Le L.T.T., Carlsen K.L., Lourenco O., Mahboub B., Mair A., Menditto E., Milenkovic B., Morais-Almeida M., Mosges R., Mullol J., Murray R., Naclerio R., Namazova-Baranova L., Novellino E., O'Hehir R.E., Ohta K., Okamoto Y., Okubo K., Onorato G.L., Palkonen S., Panzner P., Papadopoulos N.G., Park H.-S., Paulino E., Pawankar R., Pfaar O., Plavec D., Popov T.A., Potter P., Prokopakis E.P., Rottem M., Ryan D., Salimaki J., Samolinski B., Sanchez-Borges M., Schunemann H.J., Sheikh A., Sisul J.-C., Rajabian-Soderlund R., Sooronbaev T., Stellato C., To T., Todo-Bom A.-M., Tomazic P.-V., Toppila-Salmi S., Valero A., Valiulis A., Valovirta E., Ventura M.-T., Wagenmann M., Wang D.Y., Wallace D., Waserman S., Wickman M., Yorgancioglu A., Zhang L., Zhong N., Zidarn M., Zuberbier T., Aberer W., Akdis C.A., Akdis M., Alberti M.R., Almeida R., Angles R., Arnavielle S., Asayag E., Asarnoj A., Arshad H., Avolio F., Bacci E., Baiardini I., Barbara C., Barbagallo M., Baroni I., Barreto B.A., Basagana X., Bedolla-Barajas M., Beghe B., Bel E.H., Bergmann K.C., Benson M., Bertorello L., Bialoszewski A.Z., Bieber T., Bialek S., Bjermer L., Blain H., Blasi F., Blua A., Bochenska Marciniak M., Bogus-Buczynska I., Boner A.L., Bonini M., Bonini S., Bouchard J., Boulet L.P., Bourret R., Braido F., Briedis V., Brightling C.E., Bucca C., Buhl R., Buonaiuto R., Panaitescu C., Burguete Cabanas M.T., Burte E., Bush A., Caballero-Fonseca F., Caillot D., Caimmi D., Calderon M.A., Camargos P.A.M., Camuzat T., Canfora G., Carreiro-Martins P., Carriazo A.M., Carr W., Cartier C., Castellano G., Chen Y., Chiron R., Chivato T., Chkhartishvili E., Chuchalin A.G., Chung K.F., Ciaravolo M.M., Ciceran A., Cingi C., Ciprandi G., Carvalho Coehlo A.C., Colas L., Colgan E., Coll J., Conforti D., Cortes-Grimaldo R.M., Corti F., Costa-Dominguez M.C., Courbis A.L., Cox L., Crescenzo M., Custovic A., Dahlen S.E., Dario C., da Silva J., Dauvilliers Y., Darsow U., De Blay F., Dedeu T., de Fatima Emerson M., De Vries G., De Martino B., de Paula Motta Rubini N., Deleanu D., Denburg J.A., Di Capua Ercolano S., Di Carluccio N., Didier A., Dokic D., Dominguez-Silva M.G., Douagui H., Dray G., Dubakiene R., Durham S.R., Du Toit G., Eklund P., Emuzyte R., Farrell J., Farsi A., Ferreira de Mello J., Ferrero J., Fink-Wagner A., Fiocchi A., Forti S., Fuentes-Perez J.M., Galvez-Romero J.L., Gamkrelidze A., Garcia-Aymerich J., Garcia-Cobas C.Y., Garcia-Cruz M.H., Gemicioglu B., Genova S., George C., Gereda J.E., Gerth van Wijk R., Gomez R.M., Gomez-Vera J., Gonzalez Diaz S., Gotua M., Grisle I., Guidacci M., Guldemond N.A., Gutter Z., Hajjam J., Hernandez L., Hourihane J.O., Huerta-Villalobos Y.R., Humbert M., Iaccarino G., Jares E.J., Jassem E., Johnston S.L., Joos G., Jung K.S., Jutel M., Kalyoncu A.F., Karjalainen J., Kardas P., Keith P.K., Khaltaev N., Kleine-Tebbe J., Kuitunen M., Kull I., Kupczyk M., Krzych-Falta E., Lacwik P., Lauri D., Lavrut J., Lessa M., Levato G., Li J., Lieberman P., Lipiec A., Lipworth B., Lodrup Carlsen K.C., Louis R., Luna-Pech J.A., Maciej K., Magnan A., Maier D., Majer I., Malva J., Mandajieva E., Manning P., De Manuel Keenoy E., Marshall G.D., Masjedi M.R., Maspero J.F., Mathieu-Dupas E., Matta Campos J.J., Matos A.L., Maurer M., Mavale-Manuel S., Mayora O., Medina-Avalos M.A., Melen E., Melo-Gomes E., Meltzer E.O., Mercier J., Miculinic N., Mihaltan F., Moda G., Mogica-Martinez M.D., Mohammad Y., Momas I., Montefort S., Monti R., Mora Bogado D., Morato-Castro F.F., Mota-Pinto A., Moura Santo P., Munter L., Muraro A., Nadif R., Nalin M., Napoli L., Neffen H., Niedeberger V., Nekam K., Neou A., Nieto A., Nogueira-Silva L., Nogues M., Nyembue T.D., Odzhakova C., Ortega Cisneros M., Ouedraogo S., Pali-Scholl I., Papi A., Passalacqua G., Pedersen S., Pepin J.L., Pereira A.M., Persico M., Phillips J., Picard R., Pigearias B., Pin I., Pitsios C., Pohl W., Portejoie F., Pozzi A.C., Price D., Puy R., Pugin B., Pulido Ross R.E., Przemecka M., Rabe K.F., Raciborski F., Reitsma S., Ribeirinho I., Rimmer J., Rivero-Yeverino D., Rizzo J.A., Rizzo M.C., Robalo-Cordeiro C., Rodenas F., Rodo X., Rodriguez Gonzalez M., Rodriguez-Manas L., Rolland C., Rodrigues Valle S., Roman Rodriguez M., Romano A., Rodriguez-Zagal E., Rolla G., Roller-Wirnsberger R.E., Romano M., Rosado-Pinto J., Rosario N., Sagara H., Sastre-Dominguez J., Scadding G.K., Scichilone N., Schmid-Grendelmeier P., Serpa F.S., Shamai S., Sierra M., Simons F.E.R., Siroux V., Skrindo I., Sole D., Somekh D., Sondermann M., Sova M., Sorensen M., Sorlini M., Spranger O., Stelmach R., Stukas R., Sunyer J., Strozek J., Szylling A., Tebyrica J.N., Thibaudon M., Trama U., Triggiani M., Suppli Ulrik C., Urrutia-Pereira M., Valenta R., van Eerd M., van Ganse E., van Hague M., Vandenplas O., Vezzani G., Vasankari T., Vatrella A., Verissimo M.T., Viart F., Viegi M., Vicheva D., Vontetsianos T., Walker S., Werfel T., Westman M., Williams D.M., Williams S., Wilson N., Wright J., Wroczynski P., Yakovliev P., Yawn B.P., Yiallouros P.K., Yusuf O.M., Zar H.J., Zernotti M.E., Zubrinich C., Zurkuhlen A., Bousquet, Jean, Hellings, Peter W., Agache, Ioana, Amat, Flore, Annesi-Maesano, Isabella, Ansotegui, Ignacio J., Anto, Josep M., Bachert, Clau, Bateman, Eric D., Bedbrook, Anna, Bennoor, Kazi, Bewick, Mickael, Bindslev-Jensen, Carsten, Bosnic-Anticevich, Sinthia, Bosse, Isabelle, Brozek, Jan, Brussino, Luisa, Canonica, Giorgio W., Cardona, Victoria, Casale, Thoma, Cepeda Sarabia, Alfonso M., Chavannes, Niels H., Cecchi, Lorenzo, Correia de Sousa, Jaime, Costa, Elisio, Cruz, Alvaro A., Czarlewski, Wienczyslawa, De Carlo, Giuseppe, De Feo, Giulia, Demoly, Pascal, Devillier, Philippe, Dykewicz, Mark S., El-Gamal, Yehia, Eller, Esben E., Fonseca, Joao A., Fontaine, Jean-Françoi, Fokkens, Wytske J., Guzmán, Maria-Antonieta, Haahtela, Tari, Illario, Maddalena, Ivancevich, Juan-Carlo, Just, Jocelyne, Kaidashev, Igor, Khaitov, Musa, Kalayci, Omer, Keil, Thoma, Klimek, Ludger, Kowalski, Marek L., Kuna, Piotr, Kvedariene, Violeta, Larenas-Linnemann, Desiree, Laune, Daniel, Le, Lan T. T., Carlsen, Karin Lodrup, Lourenço, Olga, Mahboub, Bassam, Mair, Alpana, Menditto, Enrica, Milenkovic, Branislava, Morais-Almeida, Mario, Mösges, Ralph, Mullol, Joaquim, Murray, Ruth, Naclerio, Robert, Namazova-Baranova, Leyla, Novellino, Ettore, O'Hehir, Robyn E., Ohta, Ken, Okamoto, Yoshitaka, Okubo, Kimi, Onorato, Gabrielle L., Palkonen, Susanna, Panzner, Petr, Papadopoulos, Nikos G., Park, Hae-Sim, Paulino, Ema, Pawankar, Ruby, Pfaar, Oliver, Plavec, Davor, Popov, Ted A., Potter, Paul, Prokopakis, Emmanuel P., Rottem, Menachem, Ryan, Dermot, Salimäki, Johanna, Samolinski, Boleslaw, Sanchez-Borges, Mario, Schunemann, Holger J., Sheikh, Aziz, Sisul, Juan-Carlo, Rajabian-Söderlund, Rojin, Sooronbaev, Talant, Stellato, Cristiana, To, Teresa, Todo-Bom, Ana-Maria, Tomazic, Peter-Valentin, Toppila-Salmi, Sanna, Valero, Antonio, Valiulis, Aruna, Valovirta, Erkka, Ventura, Maria-Teresa, Wagenmann, Martin, Wang, De Yun, Wallace, Dana, Waserman, Susan, Wickman, Magnu, Yorgancioglu, Arzu, Zhang, Luo, Zhong, Nanshan, Zidarn, Mihaela, Zuberbier, Torsten, Bousquet, J., Hellings, P. W., Aberer, W., Agache, I., Akdis, C. A., Akdis, M., Alberti, M. R., Almeida, R., Amat, F., Angles, R., Annesi-Maesano, I., Ansotegui, I. J., Anto, J. M., Arnavielle, S., Asayag, E., Asarnoj, A., Arshad, H., Avolio, F., Bacci, E., Bachert, C., Baiardini, I., Barbara, C., Barbagallo, M., Baroni, I., Barreto, B. A., Basagana, X., Bateman, E. D., Bedolla-Barajas, M., Bedbrook, A., Bewick, M., Beghé, B., Bel, E. H., Bergmann, K. C., Bennoor, K. S., Benson, M., Bertorello, L., Białoszewski, A. Z., Bieber, T., Bialek, S., Bindslev-Jensen, C., Bjermer, L., Blain, H., Blasi, F., Blua, A., Bochenska Marciniak, M., Bogus-Buczynska, I., Boner, A. L., Bonini, M., Bonini, S., Bosnic-Anticevich, C. S., Bosse, I., Bouchard, J., Boulet, L. P., Bourret, R., Bousquet, P. J., Braido, F., Briedis, V., Brightling, C. E., Brozek, J., Bucca, C., Buhl, R., Buonaiuto, R., Panaitescu, C., Burguete Cabañas, M. T., Burte, E., Bush, A., Caballero-Fonseca, F., Caillot, D., Caimmi, D., Calderon, M. A., Camargos, P. A. M., Camuzat, T., Canfora, G., Canonica, G. W., Cardona, V., Carlsen, K. H., Carreiro-Martins, P., Carriazo, A. M., Carr, W., Cartier, C., Casale, T., Castellano, G., Cecchi, L., Cepeda Sarabia, A. M., Chavannes, N. H., Chen, Y., Chiron, R., Chivato, T., Chkhartishvili, E., Chuchalin, A. G., Chung, K. F., Ciaravolo, M. M., Ciceran, A., Cingi, C., Ciprandi, G., Carvalho Coehlo, A. C., Colas, L., Colgan, E., Coll, J., Conforti, D., Correia de Sousa, J., Cortés-Grimaldo, R. M., Corti, F., Costa, E., Costa-Dominguez, M. C., Courbis, A. L., Cox, L., Crescenzo, M., Cruz, A. A., Custovic, A., Czarlewski, W., Dahlen, S. E., Dario, C., da Silva, J., Dauvilliers, Y., Darsow, U., De Blay, F., De Carlo, G., Dedeu, T., de Fátima Emerson, M., De Feo, G., De Vries, G., De Martino, B., de Paula Motta Rubini, N., Deleanu, D., Demoly, P., Denburg, J. A., Devillier, P., Di Capua Ercolano, S., Di Carluccio, N., Didier, A., Dokic, D., Dominguez-Silva, M. G., Douagui, H., Dray, G., Dubakiene, R., Durham, S. R., Du Toit, G., Dykewicz, M. S., El-Gamal, Y., Eklund, P., Eller, E., Emuzyte, R., Farrell, J., Farsi, A., Ferreira de Mello, J., Ferrero, J., Fink-Wagner, A., Fiocchi, A., Fokkens, W. J., Fonseca, J. A., Fontaine, J. F., Forti, S., Fuentes-Perez, J. M., Gálvez-Romero, J. L., Gamkrelidze, A., Garcia-Aymerich, J., García-Cobas, C. Y., Garcia-Cruz, M. H., Gemicioğlu, B., Genova, S., George, C., Gereda, J. E., Gerth van Wijk, R., Gomez, R. M., Gómez-Vera, J., González Diaz, S., Gotua, M., Grisle, I., Guidacci, M., Guldemond, N. A., Gutter, Z., Guzmán, M. A., Haahtela, T., Hajjam, J., Hernández, L., Hourihane, J. O. 'B., Huerta-Villalobos, Y. R., Humbert, M., Iaccarino, G., Illario, M., Ivancevich, J. C., Jares, E. J., Jassem, E., Johnston, S. L., Joos, G., Jung, K. S., Jutel, M., Kaidashev, I., Kalayci, O., Kalyoncu, A. F., Karjalainen, J., Kardas, P., Keil, T., Keith, P. K., Khaitov, M., Khaltaev, N., Kleine-Tebbe, J., Klimek, L., Kowalski, M. L., Kuitunen, M., Kull, I., Kuna, P., Kupczyk, M., Kvedariene, V., Krzych-Fałta, E., Lacwik, P., Larenas-Linnemann, D., Laune, D., Lauri, D., Lavrut, J., Le, L. T. T., Lessa, M., Levato, G., Li, J., Lieberman, P., Lipiec, A., Lipworth, B., Lodrup Carlsen, K. C., Louis, R., Lourenço, O., Luna-Pech, J. A., Maciej, K., Magnan, A., Mahboub, B., Maier, D., Mair, A., Majer, I., Malva, J., Mandajieva, E., Manning, P., De Manuel Keenoy, E., Marshall, G. D., Masjedi, M. R., Maspero, J. F., Mathieu-Dupas, E., Matta Campos, J. J., Matos, A. L., Maurer, M., Mavale-Manuel, S., Mayora, O., Medina-Avalos, M. A., Melén, E., Melo-Gomes, E., Meltzer, E. O., Menditto, E., Mercier, J., Miculinic, N., Mihaltan, F., Milenkovic, B., Moda, G., Mogica-Martinez, M. D., Mohammad, Y., Momas, I., Montefort, S., Monti, R., Mora Bogado, D., Morais-Almeida, M., Morato-Castro, F. F., Mösges, R., Mota-Pinto, A., Moura Santo, P., Mullol, J., Münter, L., Muraro, A., Murray, R., Naclerio, R., Nadif, R., Nalin, M., Napoli, L., Namazova-Baranova, L., Neffen, H., Niedeberger, V., Nekam, K., Neou, A., Nieto, A., Nogueira-Silva, L., Nogues, M., Novellino, E., Nyembue, T. D., O'Hehir, R. E., Odzhakova, C., Ohta, K., Okamoto, Y., Okubo, K., Onorato, G. L., Ortega Cisneros, M., Ouedraogo, S., Pali-Schöll, I., Palkonen, S., Panzner, P., Papadopoulos, N. G., Park, H. S., Papi, A., Passalacqua, G., Paulino, E., Pawankar, R., Pedersen, S., Pépin, J. L., Pereira, A. M., Persico, M., Pfaar, O., Phillips, J., Picard, R., Pigearias, B., Pin, I., Pitsios, C., Plavec, D., Pohl, W., Popov, T. A., Portejoie, F., Potter, P., Pozzi, A. C., Price, D., Prokopakis, E. P., Puy, R., Pugin, B., Pulido Ross, R. E., Przemecka, M., Rabe, K. F., Raciborski, F., Rajabian-Soderlund, R., Reitsma, S., Ribeirinho, I., Rimmer, J., Rivero-Yeverino, D., Rizzo, J. A., Rizzo, M. C., Robalo-Cordeiro, C., Rodenas, F., Rodo, X., Rodriguez Gonzalez, M., Rodriguez-Mañas, L., Rolland, C., Rodrigues Valle, S., Roman Rodriguez, M., Romano, A., Rodriguez-Zagal, E., Rolla, G., Roller-Wirnsberger, R. E., Romano, M., Rosado-Pinto, J., Rosario, N., Rottem, M., Ryan, D., Sagara, H., Salimäki, J., Samolinski, B., Sanchez-Borges, M., Sastre-Dominguez, J., Scadding, G. K., Schunemann, H. J., Scichilone, N., Schmid-Grendelmeier, P., Serpa, F. S., Shamai, S., Sheikh, A., Sierra, M., Simons, F. E. R., Siroux, V., Sisul, J. C., Skrindo, I., Solé, D., Somekh, D., Sondermann, M., Sooronbaev, T., Sova, M., Sorensen, M., Sorlini, M., Spranger, O., Stellato, C., Stelmach, R., Stukas, R., Sunyer, J., Strozek, J., Szylling, A., Tebyriçá, J. N., Thibaudon, M., To, T., Todo-Bom, A., Tomazic, P. V., Toppila-Salmi, S., Trama, U., Triggiani, M., Suppli Ulrik, C., Urrutia-Pereira, M., Valenta, R., Valero, A., Valiulis, A., Valovirta, E., van Eerd, M., van Ganse, E., van Hague, M., Vandenplas, O., Ventura, M. T., Vezzani, G., Vasankari, T., Vatrella, A., Verissimo, M. T., Viart, F., Viegi, M., Vicheva, D., Vontetsianos, T., Wagenmann, M., Walker, S., Wallace, D., Wang, D. Y., Waserman, S., Werfel, T., Westman, M., Wickman, M., Williams, D. M., Williams, S., Wilson, N., Wright, J., Wroczynski, P., Yakovliev, P., Yawn, B. P., Yiallouros, P. K., Yorgancioglu, A., Yusuf, O. M., Zar, H. J., Zhang, L., Zhong, N., Zernotti, M. E., Zidarn, M., Zuberbier, T., Zubrinich, C., Zurkuhlen, A., CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Laboratory of clinical immunology, Department of Allergy and Clinical Immunology, Transylvania University of Brasov, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Epidémiologie, Systèmes d'Information, Modélisation, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Epidemiology of Allergic and Respiratory Diseases Department [iPlesp] (EPAR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Department of Allergy and Immunology, Hospital Quirónsalud Bizkaia [Bilbao], Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hacettepe University = Hacettepe Üniversitesi, Mechanobiology Institute [Singapore] (MBI), National University of Singapore (NUS), Department of Clinical Epidemiology and Biostatistics and Medicine, McMaster University [Hamilton, Ontario], Department of Dermatology [Graz, Austria], Medical University Graz, Swiss Institute of Allergy and Asthma Research (SIAF), Universität Zürich [Zürich] = University of Zurich (UZH), Department Engineering Quimica (ICEMS), Ghent University Hospital, Istituto Nazionale di Fisica Nucleare, sezione di Bari (INFN, sezione di Bari), Istituto Nazionale di Fisica Nucleare (INFN), IMIM-Hospital del Mar, Generalitat de Catalunya, University of Cape Town, Divisions of Human Genetics Infection, Inflammation and Repair, University of Southampton-School of Medicine, Centre de gérontologie, Department of Pathophysiology and Transplantation, Università degli Studi di Milano = University of Milan (UNIMI), Istituto di Geoscienze e Georisorse, Pavia, Institute of Neurobiology and Molecular Medicine, CNR, Rome, Italy and Department of Medicine-University of Naples Federico II = Università degli studi di Napoli Federico II, Woolcock Institute of Medical Research [Sydney], The University of Sydney, Université Laval [Québec] (ULaval), Departments of Clinical Epidemiology and Biostatistics and Medicine [Ontario], Service greffe de moelle osseuse, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département pneumologie et addictologie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Royal Brompton Hospital, Région Languedoc-Roussillon-Midi-Pyrénées, Vall d'Hebron University Hospital [Barcelona], University of South Florida [Tampa] (USF), Università degli Studi di Firenze = University of Florence (UniFI), University of Michigan, Department of Atmospheric, Centres de Ressources et de Compétences de la Mucoviscidose [Montpellier] (CRCM [Montpellier]), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve-Service des Maladies Respiratoires, Russian State Medical University, Universidade do Porto, Instituto de Biologia Molecular e Celular (IBMC), UCB Pharma, Colombes, Hôpital Gui de Chauliac [CHU Montpellier], CHU Strasbourg, European Federation of Allergy (EFA), Airways Diseases Patients' Associations, Università degli Studi di Salerno = University of Salerno (UNISA), Laboratoire de recherche sur les mécanismes moléculaires et pharmacologiques de l’obstruction bronchique (LOBIP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Laboratoire de Génie Informatique et Ingénierie de Production (LGI2P), IMT - MINES ALES (IMT - MINES ALES), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Linköping University (LIU), Department of Dermatology and Allergy Centre, Odense University Hospital, Vilnius University [Vilnius], Center of Research in Health Technologies and Information Systems (CINTESIS), Universidade do Porto = University of Porto, Institut d'Electronique du Solide et des Systèmes (InESS), Centre National de la Recherche Scientifique (CNRS), Son Pisa Primary Care Centre, IB-Salut Balearic Health Service, Center for Allergy and Immunology Research [Tbilisi], Department of Dermatology, Helsinki University Hospital-Skin and Allergy Hospital, Swedish Meteorological and Hydrological Institute (SMHI), CORYSS-TESS, Ukrainina Medical Stomatological Academy [Poltava, Ukraine], Institute of Social Medicine, Epidemiology and Health Economics-Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Biologie des organismes marins et écosystèmes (BOME), Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), NRC Institute of immunology FMBA, Moscow Russian federation, Allergy and Asthma Center Westend, German Society for Otorhinolaryngology HNS, Rheinische Friedrich-Wilhelms-Universität Bonn, The Institute of Environmental Medicine [Stockholm] (IMM), Karolinska Institutet [Stockholm], Medical University of Łódź (MUL), Hospital Medica Sur, Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Applied Physical Chemistry Laboratory (APCLab), Institute of Geophysics and Planetary Physics [Los Angeles] (IGPP), University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), Équipe de Recherche en Textes, Informatique, Multilinguisme (ERTIM), Institut National des Langues et Civilisations Orientales (Inalco), Institute of Oceanology [China], University of Beira Interior [Portugal] (UBI), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Pulmonary and allergy unit, American University of Sharjah-Rashid Hospital-Dubai Health Authority (DHA), Astrophysique Interprétation Modélisation (AIM (UMR7158 / UMR_E_9005 / UM_112)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Sysdiag-Modélisation et Ingénierie des Systèmes Complexes Biologiques pour le Diagnostic (SysDiag ), BIO-RAD-Centre National de la Recherche Scientifique (CNRS), 'Federico II' University of Naples Medical School, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Pneumology Department, Marius Nasta Institute of Pneumology, Department of Prevention of Environmental Hazards and Allergology, Medical University of Warsaw - Poland-Faculté de Pharmacie de Paris, Allergy and Clinical Immunology Department, Hospital CUF Descobertas, Universität zu Köln = University of Cologne, Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), Section of Otolaryngology-Head & Neck Surgery (OHNS), University of Chicago, Department of Pharmacy Naples, Université de Naples, Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital-Monash University Building, AMREP, Dept. of Electronic Engineering, Chubu University, Department of Otorhinolaryngology, Chiba University Hospital, Department of Allergology and Clinical Immunology, Charles University [Prague] (CU)-Medical Faculty in Pilsen, Department of Earth and Planetary Sciences [Cambridge, USA] (EPS), Harvard University, Allergy and Respiratory Diseases, Università degli studi di Genova = University of Genoa (UniGe), Department of Pediatrics, Nippon Medical School, Centre Hospitalier Universitaire [Grenoble] (CHU), Department of Otorhinolaryngology, Head and Neck Surgery [Mannheim, Germany], University Hospital Mannheim, Laboratoire de physique et chimie des nano-objets (LPCNO), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), CHU Grenoble, Children’s Hospital Srebrnjak [Zagreb, Croatia], Department of Physics [UMIST Manchester], University of Manchester Institute of Science and Technology (UMIST), Laboratori Nazionali del Sud (LNS), Getafe University Hospital, Madrid, Karl-Franzens-Universität Graz, Ecologie comportementale (EC), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université de Rennes (UR)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Allergy Asthma and Immunology [Haifa, Israel], Ha'Emek Medical Center, Afula-Rappaport Faculty of Medicine, University of Edinburgh, Medical University of Warsaw - Poland, Department of Allergy and Clinical Immunology [Caracas, Venezuela], Centro Médico Docente La Trinidad, Department of Computer Science [Haifa], University of Haifa [Haifa], Allergy and Respiratory Research Group, Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), National Centre of Cardiology and Internal Medicine, Ministry of Health Kyrgyz Republic, Réseau National de Surveillance Aérobiologique (RNSA), Berkeley Seismological Laboratory, Division of Clinical Immunology and Allergy, University of Naples Federico II = Università degli studi di Napoli Federico II, CIRCE, Ctr Res Energy Resources & Consumpt, Zaragoza 50018, Spain, Vilnius University Clinic of Children's Diseases, Suomen Terveystalo Allergy Clinic, Health Service and Performance Research (HESPER), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre d'EPistémologie et d'ERgologie Comparatives (CEPERC), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institute for Climate and Atmospheric Science [Leeds] (ICAS), School of Earth and Environment [Leeds] (SEE), University of Leeds-University of Leeds, Nova Southeastern University (NSU), Department of Otolaryngology, National University of Singapore (NUS)-Yong Loo Lin School of Medicine, Sachs' Children's Hospital, IAES, Department of Pulmonology, Manisa Celal Bayar University, Center for Evolutionary and Theoretical Immunology [Albuquerque, New Mexico] (CETI), The University of New Mexico [Albuquerque], National Key State Laboratory for ThermoStructural Composites (TSCM), Northwestern Polytechnical University [Xi'an] (NPU), Respiratory and Allergic Diseases, University Clinic of Respiratory and Allergic Diseases Golnik, University Hospital of Cologne [Cologne], Supported by the European Innovation Partnership on Active and Healthy Ageing and POLLAR (EIT Health, European Union)., European Project: 643803,H2020,H2020-HCO-2014,PROEIPAHA(2015), UCL - (MGD) Service de pneumologie, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Epidemiology of Allergic and Respiratory Diseases Department [Paris] (EPAR), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospital Quiròn Bizkaia Erandio, Université Pierre et Marie Curie - Paris 6 (UPMC), University of Milan, University of Naples Federico II-CNR, Rome, Italy and Department of Medicine, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Hôpital Gui de Chauliac, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Università degli Studi di Salerno (UNISA), Institut de Physique du Globe de Paris (IPGP), Centre National de la Recherche Scientifique (CNRS)-Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-IPG PARIS-Institut national des sciences de l'Univers (INSU - CNRS), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]-Epidemiology and Health Economics, Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Muséum national d'Histoire naturelle (MNHN), University of California-University of California, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Astrophysique Interprétation Modélisation (AIM (UMR_7158 / UMR_E_9005 / UM_112)), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospital CUF-Descobertas, Universität zu Köln, Medical Faculty in Pilsen-Charles University in Prague - the First Faculty of Medicine, Harvard University [Cambridge], University of Genoa (UNIGE), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), University of Graz, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université Claude Bernard Lyon 1 (UCBL), Centro Medico-Docente La Trinidad, Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Università degli studi di Napoli Federico II, Center for Evolutionary and theoretical Immunology, Biology, National Institute for Health Research, CNR, Rome, Italy and Department of Medicine-University of Naples Federico II, Institut national des sciences de l'Univers (INSU - CNRS)-IPG PARIS-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Karl-Franzens-Universität [Graz, Autriche], Department of Dermatology, Allergology and Venereology, Clinicum, University of Helsinki, Children's Hospital, Faculty of Law, HUS Children and Adolescents, HUS Inflammation Center, University Hospitals Leuven [Leuven], Universitat Pompeu Fabra [Barcelona]-Catalunya ministerio de salud, University of Zürich [Zürich] (UZH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), University of South Florida (USF), Università degli Studi di Firenze = University of Florence [Firenze], Laboratoire Magmas et Volcans (LMV), Observatoire de Physique du Globe de Clermont-Ferrand (OPGC), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), Universidade do Porto [Porto], Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin -Epidemiology and Health Economics, Université Pierre et Marie Curie - Paris 6 (UPMC)-Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre de Biologie pour la Gestion des Populations (UMR CBGP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Sondra, CentraleSupélec, Université Paris-Saclay (COmUE) (SONDRA), ONERA-CentraleSupélec-Université Paris Saclay (COmUE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), RNSA, Centre d'EPistémologie et d'ERgologie Comparatives - UMR 7304 (CEPERC), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Ear, Nose and Throat, AII - Inflammatory diseases, Pulmonology, Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), National Institute for Nuclear Physics (INFN), Université Laval, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Università degli Studi di Firenze [Firenze], University of Salerno (UNISA), Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Observatoire de Physique du Globe de Clermont-Ferrand (OPGC), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Sondra, CentraleSupélec, Université Paris-Saclay (SONDRA), ONERA-CentraleSupélec-Université Paris-Saclay, Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), École normale supérieure - Paris (ENS Paris)-Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université de Rennes 1 (UR1), Universidade do Minho, İÜC, Cerrahpaşa Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, uBibliorum, and Internal Medicine
Subjects: Allergy, Medicina Básica [Ciências Médicas], asthma -- guideline, Allergic asthma, DECISION-MAKING, Allergic Rhinitis and Its Impact on Asthma, GUIDELINES, Medical and Health Sciences, Medical Records, 0302 clinical medicine, Health care, Immunology and Allergy, 030212 general & internal medicine, asthma, Change management, rhinitis, Immunology, MASK-RHINITIS, ComputingMilieux_MISCELLANEOUS, Rinitis, mobilne aplikacije, upravljanje sprememb, Medical record, GLOBAL STRATEGY, WORK PRODUCTIVITY, Telemedicine, mobile applications, 3. Good health, Asma alérgica, rhiniti, 1107 Immunology, Ciências Médicas::Medicina Básica, klinične poti, allergic -- guideline, Life Sciences & Biomedicine, Human, PATIENT PARTICIPATION, Allergic Rhinitis, medicine.medical_specialty, animal structures, multimorbidity, EUROPEAN INNOVATION PARTNERSHIP, Change Management, [object Object], Settore MED/10 - Malattie Dell'Apparato Respiratorio, Asthma/diagnosis, CHRONIC DISEASES, MACVIA-ARIA, 03 medical and health sciences, medicine, multimorbidnost, QUALITY, Humans, critical pathways, astma -- smernica, Patient participation, Asma, udc:616.2, Asthma, Science & Technology, ARIA, business.industry, Multimorbidity, Rhinitis, Allergic, Settore MED/09 - MEDICINA INTERNA, change management, Mobile Airways Sentinel Network (MASK) Study Group, Guideline, ta3121, medicine.disease, Rinite alérgica, Rhinitis, Allergic/diagnosis, Integrated care, alergijski rinitis -- smernica, Allergic Rhinitis and Its Impact on Asthma, asthma, Change management, rhinitis, Immunology and Allergy, Immunology, 030228 respiratory system, Family medicine, 3121 General medicine, internal medicine and other clinical medicine, Medical Record, Clinical Medicine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Impact on Asthma
Abstract: Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional., EAACI -European Academy of Allergy and Clinical Immunology(undefined), info:eu-repo/semantics/acceptedVersion
Published: 2018

43. Inflammation and reactive oxygen species in status epilepticus: Biomarkers and implications for therapy

Author: Federica Frigerio, Silvia Balosso, Teresa Ravizza, Gaetano Terrone, Annamaria Vezzani, Terrone, G, Frigerio, F, Balosso, S, Ravizza, T, and Vezzani, A.
Subjects: Purinergic P2X Receptor Antagonists, Interleukin-1beta, Anti-Inflammatory Agents, Inflammation, Status epilepticus, medicine.disease_cause, Bioinformatics, Neuroprotection, 03 medical and health sciences, Behavioral Neuroscience, Epilepsy, 0302 clinical medicine, Status Epilepticus, Seizures, Medicine, Animals, Humans, 030212 general & internal medicine, Neuroinflammation, Anakinra, business.industry, Brain, medicine.disease, nervous system diseases, Febrile infection related epilepsy syndrome, Oxidative Stress, nervous system, Neurology, Neurology (clinical), medicine.symptom, business, Reactive Oxygen Species, 030217 neurology & neurosurgery, Oxidative stress, Biomarkers, medicine.drug
Abstract: Preclinical studies in immature and adult rodents and clinical observations show that neuroinflammation and oxidative stress are rapid onset phenomena occurring in the brain during status epilepticus and persisting thereafter. Notably, both neuroinflammation and oxidative stress contribute to the acute and long-term sequelae of status epilepticus thus representing potential druggable targets. Antiinflammatory drugs that interfere with the IL-1β pathway, such as anakinra, can control benzodiazepine-refractory status epilepticus in animals, and there is recent proof-of-concept evidence for therapeutic effects in children with Febrile infection related epilepsy syndrome (FIRES). Inhibitors of monoacylglycerol lipase and P2X7 receptor antagonists are also promising antiinflammatory drug candidates for rapidly aborting de novo status epilepticus and provide neuroprotection. Antiinflammatory and antioxidant drugs administered to rodents during status epilepticus and transiently thereafter, prevent long-term sequelae such as cognitive deficits and seizure progression in animals developing epilepsy. Some drugs are already in medical use and are well-tolerated, therefore, they may be considered for treating status epilepticus and its neurological consequences. Finally, markers of neuroinflammation and oxidative stress are measureable in peripheral blood and by neuroimaging, which offers an opportunity for developing prognostic and predictive mechanistic biomarkers in people exposed to status epilepticus. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures.
Published: 2019

44. Stochastic sampling effects favor manual over digital contact tracing

Author: Marco Mancastroppa, Raffaella Burioni, Alessandro Vezzani, and Claudio Castellano
Subjects: 0301 basic medicine, Physics - Physics and Society, Computer science, Epidemiology, Science, Complex networks, FOS: Physical sciences, General Physics and Astronomy, Physics and Society (physics.soc-ph), Tracing, computer.software_genre, General Biochemistry, Genetics and Molecular Biology, Article, Specimen Handling, 03 medical and health sciences, 0302 clinical medicine, Humans, 030212 general & internal medicine, Quantitative Biology - Populations and Evolution, Pandemics, Condensed Matter - Statistical Mechanics, stochastic model, Protocol (science), Stochastic Processes, Multidisciplinary, Statistical Mechanics (cond-mat.stat-mech), Stochastic process, Diagnostic Tests, Routine, SARS-CoV-2, Populations and Evolution (q-bio.PE), Sampling (statistics), COVID-19, General Chemistry, Complex network, Models, Theoretical, Network dynamics, 030104 developmental biology, FOS: Biological sciences, Scalability, Quarantine, Data mining, Contact Tracing, computer, Contact tracing, Algorithms
Abstract: Isolation of symptomatic individuals, tracing and testing of their nonsymptomatic contacts are fundamental strategies for mitigating the current COVID-19 pandemic. The breaking of contagion chains relies on two complementary strategies: manual reconstruction of contacts based on interviews and a digital (app-based) privacy-preserving contact tracing. We compare their effectiveness using model parameters tailored to describe SARS-CoV-2 diffusion within the activity-driven model, a general empirically validated framework for network dynamics. We show that, even for equal probability of tracing a contact, manual tracing robustly performs better than the digital protocol, also taking into account the intrinsic delay and limited scalability of the manual procedure. This result is explained in terms of the stochastic sampling occurring during the case-by-case manual reconstruction of contacts, contrasted with the intrinsically prearranged nature of digital tracing, determined by the decision to adopt the app or not by each individual. The better performance of manual tracing is enhanced by heterogeneity in agent behavior: superspreaders not adopting the app are completely invisible to digital contact tracing, while they can be easily traced manually, due to their multiple contacts. We show that this intrinsic difference makes the manual procedure dominant in realistic hybrid protocols., Comment: Main document: 11 pages, 6 figures; Supplementary Information: 18 pages, 5 figures
Published: 2020

45. Mitochondria as the decision makers for cancer cell fate: from signaling pathways to therapeutic strategies

Author: Paolo Pinton, Alberto Danese, Bianca Vezzani, Stefano Pelucchi, Carlotta Giorgi, Lorenzo Modesti, Veronica Angela Maria Vitto, Virginia Corazzi, and Ilaria Genovese
Subjects: 0301 basic medicine, Cell type, Physiology, bioenergetics, Ca2+ signaling, cancer, cGAS-cGAMP-STING pathway, Mitochondria, mitophagy, Mitochondrion, Biology, Cell fate determination, NO, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, Mitophagy, medicine, Animals, Humans, Cell Lineage, Calcium Signaling, Molecular Biology, Endoplasmic reticulum, Cancer, Cell Biology, medicine.disease, Cell biology, 030104 developmental biology, Cancer cell, Signal transduction, Energy Metabolism, 030217 neurology & neurosurgery, Signal Transduction
Abstract: As pivotal players in cellular metabolism, mitochondria have a double-faceted role in the final decision of cell fate. This is true for all cell types, but it is even more important and intriguing in the cancer setting. Mitochondria regulate cell fate in many diverse ways: through metabolism, by producing ATP and other metabolites deemed vital or detrimental for cancer cells; through the regulation of Ca2+ homeostasis, especially by the joint participation of the endoplasmic reticulum in a membranous tethering system for Ca2+ signaling called mitochondria-ER associated membranes (MAMs); and by regulating signaling pathways involved in the survival of cancer cells such as mitophagy. Recent studies have shown that mitochondria can also play a role in the regulation of inflammatory pathways in cancer cells, for example, through the release of mitochondrial DNA (mtDNA) involved in the activation of the cGAS-cGAMP-STING pathway. In this review, we aim to explore the role of mitochondria as decision makers in fostering cancer cell death or survival depending on the tumor cell stage and describe novel anticancer therapeutic strategies targeting mitochondria.
Published: 2020

46. Drug Resistance in Epilepsy: Clinical Impact, Potential Mechanisms, and New Innovative Treatment Options

Author: Wolfgang, Löscher, Heidrun, Potschka, Sanjay M, Sisodiya, and Annamaria, Vezzani
Subjects: Epilepsy, Drug Resistance, Animals, Humans, Anticonvulsants, Review Articles, Randomized Controlled Trials as Topic
Abstract: Epilepsy is a chronic neurologic disorder that affects over 70 million people worldwide. Despite the availability of over 20 antiseizure drugs (ASDs) for symptomatic treatment of epileptic seizures, about one-third of patients with epilepsy have seizures refractory to pharmacotherapy. Patients with such drug-resistant epilepsy (DRE) have increased risks of premature death, injuries, psychosocial dysfunction, and a reduced quality of life, so development of more effective therapies is an urgent clinical need. However, the various types of epilepsy and seizures and the complex temporal patterns of refractoriness complicate the issue. Furthermore, the underlying mechanisms of DRE are not fully understood, though recent work has begun to shape our understanding more clearly. Experimental models of DRE offer opportunities to discover, characterize, and challenge putative mechanisms of drug resistance. Furthermore, such preclinical models are important in developing therapies that may overcome drug resistance. Here, we will review the current understanding of the molecular, genetic, and structural mechanisms of ASD resistance and discuss how to overcome this problem. Encouragingly, better elucidation of the pathophysiological mechanisms underpinning epilepsies and drug resistance by concerted preclinical and clinical efforts have recently enabled a revised approach to the development of more promising therapies, including numerous potential etiology-specific drugs ("precision medicine") for severe pediatric (monogenetic) epilepsies and novel multitargeted ASDs for acquired partial epilepsies, suggesting that the long hoped-for breakthrough in therapy for as-yet ASD-resistant patients is a feasible goal. SIGNIFICANCE STATEMENT: Drug resistance provides a major challenge in epilepsy management. Here, we will review the current understanding of the molecular, genetic, and structural mechanisms of drug resistance in epilepsy and discuss how the problem might be overcome.
Published: 2020

47. The role of mitochondria-associated membranes in cellular homeostasis and diseases

Author: Mariasole, Perrone, Natascia, Caroccia, Ilaria, Genovese, Sonia, Missiroli, Lorenzo, Modesti, Gaia, Pedriali, Bianca, Vezzani, Veronica Angela Maria, Vitto, Michele, Antenori, Magdalena, Lebiedzinska-Arciszewska, Mariusz R, Wieckowski, Carlotta, Giorgi, and Paolo, Pinton
Subjects: Neoplasms, Mitochondrial Membranes, Diabetes Mellitus, Animals, Homeostasis, Humans, Neurodegenerative Diseases, Mitochondria
Abstract: Mitochondria and endoplasmic reticulum (ER) are fundamental in the control of cell physiology regulating several signal transduction pathways. They continuously communicate exchanging messages in their contact sites called MAMs (mitochondria-associated membranes). MAMs are specific microdomains acting as a platform for the sorting of vital and dangerous signals. In recent years increasing evidence reported that multiple scaffold proteins and regulatory factors localize to this subcellular fraction suggesting MAMs as hotspot signaling domains. In this review we describe the current knowledge about MAMs' dynamics and processes, which provided new correlations between MAMs' dysfunctions and human diseases. In fact, MAMs machinery is strictly connected with several pathologies, like neurodegeneration, diabetes and mainly cancer. These pathological events are characterized by alterations in the normal communication between ER and mitochondria, leading to deep metabolic defects that contribute to the progression of the diseases.
Published: 2020

48. Interorganellar calcium signaling in the regulation of cell metabolism: A cancer perspective

Author: Saverio Marchi, Mariusz R. Wieckowski, Paolo Pinton, Carlotta Giorgi, Anna Tarocco, Alessandro Rimessi, Bianca Vezzani, and Gaia Pedriali
Subjects: 0301 basic medicine, Ca2+ signaling, Cancer, Interorganellar communication, Metabolism, Cellular homeostasis, Socio-culturale, Mitochondrion, Biology, Cell fate determination, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, Organelle, Animals, Homeostasis, Humans, Calcium Signaling, Cellular compartment, Calcium signaling, Organelles, Endoplasmic reticulum, Cell Biology, Cell biology, 030104 developmental biology, Cell metabolism, Calcium, 030217 neurology & neurosurgery, Developmental Biology
Abstract: Organelles were originally considered to be individual cellular compartments with a defined organization and function. However, recent studies revealed that organelles deeply communicate within each other via Ca2+ exchange. This communication, mediated by specialized membrane regions in close apposition between two organelles, regulate cellular functions, including metabolism and cell fate decisions. Advances in microscopy techniques, molecular biology and biochemistry have increased our understanding of these interorganelle platforms. Research findings suggest that interorganellar Ca2+ signaling, which is altered in cancer, influences tumorigenesis and tumor progression by controlling cell death programs and metabolism. Here, we summarize the available data on the existence and composition of interorganelle platforms connecting the endoplasmic reticulum with mitochondria, the plasma membrane, or endolysosomes. Finally, we provide a timely overview of the potential function of interorganellar Ca2+ signaling in maintaining cellular homeostasis.
Published: 2020

49. Hyperbaric Oxygen Treatment for Carbon Monoxide Poisoning in Italy: Retrospective Validation of a Data Collection Tool for the Italian Registry of Carbon Monoxide Poisonings (IRCOP)

Author: Lidio Maffi, Gerardo Bosco, Antonios Soumelis, Matteo Paganini, Giuliano Vezzani, and Enrico M. Camporesi
Subjects: Adult, Male, medicine.medical_specialty, Injury control, Adolescent, Health, Toxicology and Mutagenesis, arterial blood gas analysis, lcsh:Medicine, Poison control, Article, carbon monoxide, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Hyperbaric oxygen, Retrospective analysis, Medicine, Humans, 030212 general & internal medicine, Registries, Child, Aged, Retrospective Studies, Aged, 80 and over, Hyperbaric Oxygenation, Data collection, business.industry, Carbon monoxide poisoning, carbon monoxide poisoning, Data Collection, lcsh:R, Public Health, Environmental and Occupational Health, Infant, Newborn, Infant, Emergency department, CO poisoning, Middle Aged, medicine.disease, hyperbaric oxygen therapy, 030228 respiratory system, Italy, Child, Preschool, Emergency medicine, Female, business
Abstract: Background: Carbon Monoxide (CO) poisoning is a frequent cause of intoxication. However, CO poisoning incidence is globally underreported, as well as its features, especially in Italy. The aim of this study was to investigate such characteristics of CO intoxication and foster the creation of the Italian Registry of Carbon Monoxide Poisonings. Methods: A data collection tool was developed and organized in five sections: Patient&rsquo, s characteristics, CO intoxication modality, emergency medical service and emergency department, hyperbaric facility, outcomes. The tool was validated through a retrospective analysis, including CO intoxicated patients treated in 14 Italian hyperbaric facilities between 2015 and 2016. Results: A total of 1383 patients were included. The high completion ratio (85%) of the collection tool suggests its feasibility in practical terms. CO intoxications were mostly accidental (93.64%) and caused by solid fuel (48.59%). There was not a uniform application of hyperbaric oxygen treatment protocols, but most of the patients were adequately treated at least at 2.5 ATA for more than 60 min (44.97%). Conclusion: This analysis provided new information that was previously unavailable in this country. Furthermore, this tool proved to be a valid base for future registry aiming to consolidate the body of knowledge about CO intoxications in Italy.
Published: 2020

50. Hyperbaric oxygen therapy ameliorates osteonecrosis in patients by modulating inflammation and oxidative stress

Author: Garrett Enten, Abdullah Abou-Samra, Simona Mrakic Sposta, Sandro Malacrida, Alessandra Vezzoli, Alex Rizzato, Gerardo Bosco, Enrico M. Camporesi, Giuliano Vezzani, and Silvia Quartesan
Subjects: 0301 basic medicine, Male, Interleukin-1beta, Avascular necrosis, medicine.disease_cause, Oxygen, 0302 clinical medicine, Femur Head Necrosis, Drug Discovery, Medicine, chemistry.chemical_classification, Hyperbaric Oxygenation, biology, General Medicine, IL-1?, IL-6, Reactive oxygen species, TNF-?, femoral head necrosis, Middle Aged, medicine.anatomical_structure, IL-1β, 030220 oncology & carcinogenesis, Anesthesia, Tumor necrosis factor alpha, medicine.symptom, Inflammation Mediators, Research Paper, Adult, chemistry.chemical_element, Inflammation, IL–6, TNF-α, Biomarkers, Humans, Interleukin-6, Reactive Oxygen Species, Tumor Necrosis Factor-alpha, Oxidative Stress, Pharmacology, Drug Discovery3003 Pharmaceutical Science, 03 medical and health sciences, Femoral head, Interleukin 6, business.industry, lcsh:RM1-950, medicine.disease, lcsh:Therapeutics. Pharmacology, 030104 developmental biology, chemistry, biology.protein, business, Oxidative stress
Abstract: Early stages of avascular necrosis of the femoral head (AVNFH) can be conservatively treated with hyperbaric oxygen therapy (HBOT). This study investigated how HBOT modulates inflammatory markers and reactive oxygen species (ROS) in patients with AVNFH. Twenty-three male patients were treated with two cycles of HBOT, 30 sessions each with a 30 days break between cycles. Each session consisted of 90 minutes of 100% inspired oxygen at 2.5 absolute atmospheres of pressure. Plasma levels of tumor necrosis factor alfa (TNF-α), interleukin 6 (IL-6), interleukin 1 beta (IL-1β) and ROS production were measured before treatment (T0), after 15 and 30 HBOT sessions (T1 and T2), after the 30-day break (T3), and after 60 sessions (T4). Results showed a significant reduction in TNF-α and IL-6 plasma levels over time. This decrease in inflammatory markers mirrored observed reductions in bone marrow edema and reductions in patient self-reported pain.
Published: 2018

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