|
1
|
Tüsüz Önata E, Özdemir Ö. Fecal microbiota transplantation in allergic diseases. World J Methodol 2025; 15:101430. [DOI: 10.5662/wjm.v15.i2.101430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Revised: 10/17/2024] [Accepted: 11/01/2024] [Indexed: 11/27/2024] Open
Abstract
Microorganisms such as bacteria, fungi, viruses, parasites living in the human intestine constitute the human intestinal microbiota. Dysbiosis refers to compositional and quantitative changes that negatively affect healthy gut microbiota. In recent years, with the demonstration that many diseases are associated with dysbiosis, treatment strategies targeting the correction of dysbiosis in the treatment of these diseases have begun to be investigated. Faecal microbiota transplantation (FMT) is the process of transferring faeces from a healthy donor to another recipient in order to restore the gut microbiota and provide a therapeutic benefit. FMT studies have gained popularity after probiotic, prebiotic, symbiotic studies in the treatment of dysbiosis and related diseases. FMT has emerged as a potential new therapy in the treatment of allergic diseases as it is associated with the maintenance of intestinal microbiota and immunological balance (T helper 1/T helper 2 cells) and thus suppression of allergic responses. In this article, the definition, application, safety and use of FMT in allergic diseases will be discussed with current data.
Collapse
Affiliation(s)
- Ece Tüsüz Önata
- Division of Pediatric Allergy and Immunology, Medical Faculty, Sakarya University, Adapazarı 54100, Sakarya, Türkiye
| | - Öner Özdemir
- Division of Pediatric Allergy and Immunology, Medical Faculty, Sakarya University, Adapazarı 54100, Sakarya, Türkiye
| |
Collapse
|
|
2
|
Çeliksoy MH, Naiboglu S, Topal E, Karadağ ŞİK, Yılmaz E, Bologur H. The effect of formula type on the prognosis of allergic proctocolitis due to cow's milk allergy. Allergol Immunopathol (Madr) 2025; 53:126-130. [PMID: 39786885 DOI: 10.15586/aei.v53i1.1240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2024] [Accepted: 11/12/2024] [Indexed: 01/12/2025]
Abstract
BACKGROUND Food protein-induced allergic proctocolitis is a nonimmunoglobulin E-mediated, self-limited food allergy of the rectum and the colon. Cow's milk protein is the most common allergen responsible for the disease. OBJECTIVE This study aimed to investigate the roles of different types of formulas in building early tolerance to food protein-induced allergic proctocolitis in infants. METHODS The medical records of 45 pediatric patients diagnosed with proctocolitis due to cow's milk allergy between August 2021 and August 2023 and whose disease progression was followed in three tertiary care centers were reviewed retrospectively. RESULTS The study included 45 patients who were diagnosed with proctocolitis due to cow's milk allergy (24 males, 21 females; median age: 4 months). Among them, 24 patients were fed an amino acid-based formula, and 21 (46.7%) patients were fed an extensively hydrolyzed formula. The average age of acquisition of cow's milk tolerance was lower in the group fed with the amino acid-based formula than in the group fed with extensively hydrolyzed formula (P = 0.038). Furthermore, the group fed with amino acid-based formula had a shorter tolerance period than the group fed with the extensively hydrolyzed formula group (P = 0.044). CONCLUSION Compared to an extensively hydrolyzed formula, an amino acid-based formula led to the early development of tolerance in children with allergic proctocolitis induced by cow's milk.
Collapse
Affiliation(s)
- Mehmet Halil Çeliksoy
- Department of Pediatric Allergy and Immunology, Basaksehir Cam and Sakura City Hospital, University of Health Sciences, Istanbul, Turkey;
| | - Sezin Naiboglu
- Department of Pediatric Allergy and Immunology, Basaksehir Cam and Sakura City Hospital, University of Health Sciences, Istanbul, Turkey
| | - Erdem Topal
- Medical Faculty, Pediatric Allergy and Immunology, Inonu University, Malatya, Turkey
| | - Şefika İlknur Kökçü Karadağ
- Department of Pediatric Allergy and Immunology, Cemil Tascioglu City Hospital, University of Health Sciences, Istanbul, Turkey
| | - Ercan Yılmaz
- Medical Faculty, Pediatric Allergy and Immunology, Inonu University, Malatya, Turkey
| | - Hamit Bologur
- Department of Pediatric Allergy and Immunology, Cemil Tascioglu City Hospital, University of Health Sciences, Istanbul, Turkey
| |
Collapse
|
|
3
|
Zhang X, Chen X, Bai T, Meng X, Wu Y, Yang A, Chen H, Li X. Egg White Diet Induces Severe Allergic Enteritis in an Animal Model Driven by Caspase-3 and Gasdermin C-Mediated Mucosal Alarmin Secretion. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2024; 72:24035-24045. [PMID: 39420749 DOI: 10.1021/acs.jafc.4c06967] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/19/2024]
Abstract
Allergic enteritis is an important phenotype of food allergies. However, there is not a suitable animal model for deeply exploring the natural progression and mechanism of allergic enteritis. In our study, we successfully developed an allergic enteritis animal model by feeding mice with an egg white diet. Following the dietary challenge, allergic mice displayed typical food allergy manifestations, including decreased core temperature, aversion to the allergenic diet, and elevated levels of serum sIgE and mMCP-1. Notably, these dietary challenged mice exhibited severe gut damage, characterized by disrupted intestinal microstructure, tissue inflammation, and edema that were evident morphologically. Moreover, upon exposure to food allergens, we observed a marked increase in caspase-3 and GSDMC levels in allergic mice. These two active proteins were found to be colocalized in damaged mucosal enterocytes and were associated with the secretion of epithelial sourced alarmins, such as IL25 and TSLP. Further data on the cellular and molecular levels suggest that such severe food-induced enteritis is mediated by the caspase-3-GSDMC pathway. We believe that this established animal model provides a valuable tool for advancing research on the mechanisms of food allergies.
Collapse
Affiliation(s)
- Xing Zhang
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, P. R. China
- School of Food Science and Technology, Nanchang University, Nanchang 330047, P. R. China
- Sino-German Joint Research Institute, Nanchang University, Nanchang 330047, P. R. China
| | - Xiao Chen
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, P. R. China
- School of Food Science and Technology, Nanchang University, Nanchang 330047, P. R. China
- Sino-German Joint Research Institute, Nanchang University, Nanchang 330047, P. R. China
| | - Tianliang Bai
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, P. R. China
- School of Food Science and Technology, Nanchang University, Nanchang 330047, P. R. China
- Sino-German Joint Research Institute, Nanchang University, Nanchang 330047, P. R. China
| | - Xuanyi Meng
- Sino-German Joint Research Institute, Nanchang University, Nanchang 330047, P. R. China
- Jiangxi Province Key Laboratory of Food Allergy, Nanchang University, Nanchang 330047, P. R. China
| | - Yong Wu
- Sino-German Joint Research Institute, Nanchang University, Nanchang 330047, P. R. China
- Jiangxi Province Key Laboratory of Food Allergy, Nanchang University, Nanchang 330047, P. R. China
| | - Anshu Yang
- Sino-German Joint Research Institute, Nanchang University, Nanchang 330047, P. R. China
- Jiangxi Province Key Laboratory of Food Allergy, Nanchang University, Nanchang 330047, P. R. China
| | - Hongbing Chen
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, P. R. China
- School of Food Science and Technology, Nanchang University, Nanchang 330047, P. R. China
- Sino-German Joint Research Institute, Nanchang University, Nanchang 330047, P. R. China
- Jiangxi Province Key Laboratory of Food Allergy, Nanchang University, Nanchang 330047, P. R. China
| | - Xin Li
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, P. R. China
- School of Food Science and Technology, Nanchang University, Nanchang 330047, P. R. China
- Sino-German Joint Research Institute, Nanchang University, Nanchang 330047, P. R. China
| |
Collapse
|
|
4
|
Zhang X, Chen X, Yang F, Shao H, Bai T, Meng X, Wu Y, Yang A, Chen H, Li X. Extracellular adenosine triphosphate skews the T helper cell balance and enhances neutrophil activation in mice with food allergies. Food Funct 2024; 15:5641-5654. [PMID: 38726659 DOI: 10.1039/d4fo01135j] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/21/2024]
Abstract
Exposure to food allergens elicits fast changes in the intestinal microenvironment, which guides the development of allergic reactions. Investigating the key information about these changes may help in better understanding food allergies. In this research, we explored the relationship between a food allergy and extracellular adenosine triphosphate (ATP), a danger molecule that has been proved to regulate the onset of allergic asthma and dermatitis but has not been studied in food allergies, by developing a unique animal model through allergen-containing diet feeding. After consuming an allergen-containing diet for 7 days, the allergic mice exhibited severe enteritis with elevated luminal ATP levels. The dysregulated luminal ATP worsened food-induced enteritis by enhancing Th17 cell responses and increasing mucosal neutrophil accumulation. In vitro experiments demonstrated that ATP intervention facilitated Th17 cell differentiation and neutrophil activation. In addition, the diet-induced allergy showed noticeable gut dysbiosis, characterized by decreased microbial diversity and increased diet-specific microbiota signatures. As the first, we show that food-induced enteritis is associated with an elevated concentration of luminal ATP. The dysregulated extracellular ATP exacerbated the enteritis of mice to a food challenge by manipulating intestinal Th17 cells and neutrophils.
Collapse
Affiliation(s)
- Xing Zhang
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, P.R. China.
- School of Food Science and Technology, Nanchang University, Nanchang 330047, P.R. China
- Sino-German Joint Research Institute, Nanchang University, Nanchang 330047, P.R. China
| | - Xiao Chen
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, P.R. China.
- School of Food Science and Technology, Nanchang University, Nanchang 330047, P.R. China
- Sino-German Joint Research Institute, Nanchang University, Nanchang 330047, P.R. China
| | - Fan Yang
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, P.R. China.
- School of Food Science and Technology, Nanchang University, Nanchang 330047, P.R. China
- Sino-German Joint Research Institute, Nanchang University, Nanchang 330047, P.R. China
| | - Huming Shao
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, P.R. China.
- School of Food Science and Technology, Nanchang University, Nanchang 330047, P.R. China
- Sino-German Joint Research Institute, Nanchang University, Nanchang 330047, P.R. China
| | - Tianliang Bai
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, P.R. China.
- School of Food Science and Technology, Nanchang University, Nanchang 330047, P.R. China
- Sino-German Joint Research Institute, Nanchang University, Nanchang 330047, P.R. China
| | - Xuanyi Meng
- Sino-German Joint Research Institute, Nanchang University, Nanchang 330047, P.R. China
- Jiangxi Province Key Laboratory of Food Allergy, Nanchang University, Nanchang 330047, China
| | - Yong Wu
- Sino-German Joint Research Institute, Nanchang University, Nanchang 330047, P.R. China
- Jiangxi Province Key Laboratory of Food Allergy, Nanchang University, Nanchang 330047, China
| | - Anshu Yang
- Sino-German Joint Research Institute, Nanchang University, Nanchang 330047, P.R. China
- Jiangxi Province Key Laboratory of Food Allergy, Nanchang University, Nanchang 330047, China
| | - Hongbing Chen
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, P.R. China.
- School of Food Science and Technology, Nanchang University, Nanchang 330047, P.R. China
- Sino-German Joint Research Institute, Nanchang University, Nanchang 330047, P.R. China
- Jiangxi Province Key Laboratory of Food Allergy, Nanchang University, Nanchang 330047, China
| | - Xin Li
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, P.R. China.
- School of Food Science and Technology, Nanchang University, Nanchang 330047, P.R. China
- Sino-German Joint Research Institute, Nanchang University, Nanchang 330047, P.R. China
| |
Collapse
|
|
5
|
Blanco‐Pérez F, Gonzalez‐Menendez I, Stassen M, Kato Y, Laiño J, Kirberg J, Krause M, Martella M, Shibata N, Quintanilla‐Martinez L, Feyerabend TB, Rodewald H, Galli SJ, Vieths S, Scheurer S, Toda M. Mast cells partly contribute to allergic enteritis development: Findings in two different mast cell-deficient mice. Allergy 2022; 77:1051-1054. [PMID: 34807472 DOI: 10.1111/all.15182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Revised: 10/15/2021] [Accepted: 11/04/2021] [Indexed: 11/27/2022]
Affiliation(s)
- Frank Blanco‐Pérez
- Vice President Research Group “Molecular Allergology”, Paul‐Ehrlich‐Institut Langen Germany
| | - Irene Gonzalez‐Menendez
- Institute of Pathology and Neuropathology, Comprehensive Cancer Center University Hospital Tübingen, Eberhard Karls University of Tübingen Tübingen Germany
| | - Michael Stassen
- Institute for Immunology and Research Center for Immunotherapy (FZI) University Medical Center of the Johannes Gutenberg University Mainz Germany
| | - Yoichiro Kato
- Department of Pathology Tokyo Women's Medical University Tokyo Japan
| | - Jonathan Laiño
- Vice President Research Group “Molecular Allergology”, Paul‐Ehrlich‐Institut Langen Germany
| | - Jörg Kirberg
- Division of Immunology Paul‐Ehrlich‐Institut Langen Germany
| | - Maren Krause
- Vice President Research Group “Molecular Allergology”, Paul‐Ehrlich‐Institut Langen Germany
| | - Manuela Martella
- Institute of Pathology and Neuropathology, Comprehensive Cancer Center University Hospital Tübingen, Eberhard Karls University of Tübingen Tübingen Germany
| | - Noriyuki Shibata
- Department of Pathology Tokyo Women's Medical University Tokyo Japan
| | - Leticia Quintanilla‐Martinez
- Institute of Pathology and Neuropathology, Comprehensive Cancer Center University Hospital Tübingen, Eberhard Karls University of Tübingen Tübingen Germany
| | | | - Hans‐Reimer Rodewald
- Division of Cellular Immunology German Cancer Research Center (DKFZ) Heidelberg Germany
| | - Stephen J. Galli
- Department of Pathology The Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine Stanford California USA
- Department of Microbiology and Immunology Stanford University School of Medicine Stanford California USA
| | - Stefan Vieths
- Vice President Research Group “Molecular Allergology”, Paul‐Ehrlich‐Institut Langen Germany
| | - Stephan Scheurer
- Vice President Research Group “Molecular Allergology”, Paul‐Ehrlich‐Institut Langen Germany
| | - Masako Toda
- Vice President Research Group “Molecular Allergology”, Paul‐Ehrlich‐Institut Langen Germany
- Laboratory of Food and Biomolecular Science, Graduate School of Agricultural Science Tohoku University Sendai Japan
| |
Collapse
|
|
6
|
Mennini M, Fiocchi AG, Cafarotti A, Montesano M, Mauro A, Villa MP, Di Nardo G. Food protein-induced allergic proctocolitis in infants: Literature review and proposal of a management protocol. World Allergy Organ J 2020; 13:100471. [PMID: 33072241 PMCID: PMC7549143 DOI: 10.1016/j.waojou.2020.100471] [Citation(s) in RCA: 64] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Revised: 09/12/2020] [Accepted: 09/14/2020] [Indexed: 02/06/2023] Open
Abstract
Food protein-induced allergic proctocolitis (FPIAP) is a condition characterized by inflammatory changes in the distal colon in response to one or more foreign food proteins because of immune-mediated reactions. FPIAP prevalence estimates range widely from 0.16% in healthy children and 64% in patients with blood in stools. In clinical practice, FPIAP is diagnosed when patients respond positively to the elimination of a suspected triggering food allergen. Nevertheless, significant proportions of infants get misdiagnosed with IgE mediated allergy and undergo unnecessary dietary changes. Diagnosis is based on clinical symptoms, a good response to an allergen-free diet and the recurrence of symptoms during the "allergy challenge test". Sometimes clinical features may be non-specific and the etiology of rectal bleeding in childhood may be heterogeneous. Therefore, it is crucial to exclude a variety of other possible causes of rectal bleeding in the pediatric age group, including infection, anal fissure, intestinal intussusception and, in infants, necrotizing enterocolitis and very early onset inflammatory bowel disease. The diagnostic workup includes in those cases invasive procedures such as sigmoidoscopy and colonoscopy with biopsies. The high prevalence of FPIAP contrasts with the lack of known information about the pathogenesis of this condition. For this reason and due to the absence of a review of the evidence, a literature review appears necessary to clarify some aspects of allergic colitis. The aim of the review is to fill this gap and to lay the foundations for a subsequent evidence-based approach to the condition.
Collapse
Affiliation(s)
- Maurizio Mennini
- Multifactorial and Systemic Diseases Research Area, Predictive and Preventive Medicine Research Unit, Division of Allergy Bambino Gesù Children's Hospital IRCCS, Rome, Italy
| | - Alessandro Giovanni Fiocchi
- Multifactorial and Systemic Diseases Research Area, Predictive and Preventive Medicine Research Unit, Division of Allergy Bambino Gesù Children's Hospital IRCCS, Rome, Italy
| | - Arianna Cafarotti
- Multifactorial and Systemic Diseases Research Area, Predictive and Preventive Medicine Research Unit, Division of Allergy Bambino Gesù Children's Hospital IRCCS, Rome, Italy
| | - Marilisa Montesano
- Chair of Pediatrics, NESMOS Department, Faculty of Medicine and Psychology, Sapienza University of Rome, Sant’Andrea University Hospital, Rome, Italy
| | - Angela Mauro
- Department of Paediatrics, Santobono-Pausilipon Children's Hospital, Naples, Italy
| | - Maria Pia Villa
- Chair of Pediatrics, NESMOS Department, Faculty of Medicine and Psychology, Sapienza University of Rome, Sant’Andrea University Hospital, Rome, Italy
| | - Giovanni Di Nardo
- Chair of Pediatrics, NESMOS Department, Faculty of Medicine and Psychology, Sapienza University of Rome, Sant’Andrea University Hospital, Rome, Italy
| |
Collapse
|
|
7
|
Blanco-Pérez F, Kato Y, Gonzalez-Menendez I, Laiño J, Ohbayashi M, Burggraf M, Krause M, Kirberg J, Iwakura Y, Martella M, Quintanilla-Martinez L, Shibata N, Vieths S, Scheurer S, Toda M. CCR8 leads to eosinophil migration and regulates neutrophil migration in murine allergic enteritis. Sci Rep 2019; 9:9608. [PMID: 31270368 PMCID: PMC6610106 DOI: 10.1038/s41598-019-45653-7] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2019] [Accepted: 06/12/2019] [Indexed: 02/06/2023] Open
Abstract
Allergic enteritis (AE) is a gastrointestinal form of food allergy. This study aimed to elucidate cellular and molecular mechanisms of AE using a murine model. To induce AE, BALB/c wild type (WT) mice received intraperitoneal sensitization with ovalbumin (an egg white allergen) plus ALUM and feeding an egg white (EW) diet. Microarray analysis showed enhanced gene expression of CC chemokine receptor (CCR) 8 and its ligand, chemokine CC motif ligand (CCL) 1 in the inflamed jejunum. Histological and FACS analysis showed that CCR8 knock out (KO) mice exhibited slightly less inflammatory features, reduced eosinophil accumulation but accelerated neutrophil accumulation in the jejunums, when compared to WT mice. The concentrations of an eosinophil chemoattractant CCL11 (eotaxin-1), but not of IL-5, were reduced in intestinal homogenates of CCR8KO mice, suggesting an indirect involvement of CCR8 in eosinophil accumulation in AE sites by inducing CCL11 expression. The potential of CCR8 antagonists to treat allergic asthma has been discussed. However, our results suggest that CCR8 blockade may promote neutrophil accumulation in the inflamed intestinal tissues, and not be a suitable therapeutic target for AE, despite the potential to reduce eosinophil accumulation. This study advances our knowledge to establish effective anti-inflammatory strategies in AE treatment.
Collapse
Affiliation(s)
- Frank Blanco-Pérez
- Vice President Research Group "Molecular Allergology", Paul-Ehrlich-Institut, Langen, Germany
| | - Yoichiro Kato
- Department of Pathology, Tokyo Women's Medical University, Tokyo, Japan
| | - Irene Gonzalez-Menendez
- Institute of Pathology and Neuropathology, Eberhard Karls University of Tübingen and Comprehensive Cancer Center, University Hospital Tübingen, Tübingen, Germany
| | - Jonathan Laiño
- Vice President Research Group "Molecular Allergology", Paul-Ehrlich-Institut, Langen, Germany
| | - Masaharu Ohbayashi
- Department of Nursing, Graduate School of Health Sciences, Toyohashi SOZO University, Toyohashi, Japan
| | - Manja Burggraf
- Junior Research Group 1 Experimental Allergy Models", Paul-Ehrlich-Institut, Langen, Germany
| | - Maren Krause
- Vice President Research Group "Molecular Allergology", Paul-Ehrlich-Institut, Langen, Germany
| | - Jörg Kirberg
- Division of Immunology, Paul-Ehrlich-Institut, Langen, Germany
| | - Yoichiro Iwakura
- Center for Animal Disease Models, Research Institute for Biomedical Sciences (RIBS), Tokyo University of Science (TUS), Chiba, Japan
| | - Manuela Martella
- Institute of Pathology and Neuropathology, Eberhard Karls University of Tübingen and Comprehensive Cancer Center, University Hospital Tübingen, Tübingen, Germany
| | - Leticia Quintanilla-Martinez
- Institute of Pathology and Neuropathology, Eberhard Karls University of Tübingen and Comprehensive Cancer Center, University Hospital Tübingen, Tübingen, Germany
| | - Noriyuki Shibata
- Department of Pathology, Tokyo Women's Medical University, Tokyo, Japan
| | - Stefan Vieths
- Vice President Research Group "Molecular Allergology", Paul-Ehrlich-Institut, Langen, Germany
| | - Stephan Scheurer
- Vice President Research Group "Molecular Allergology", Paul-Ehrlich-Institut, Langen, Germany
| | - Masako Toda
- Vice President Research Group "Molecular Allergology", Paul-Ehrlich-Institut, Langen, Germany. .,Junior Research Group 1 Experimental Allergy Models", Paul-Ehrlich-Institut, Langen, Germany. .,Laboratory of Food and Biomolecular Science, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
| |
Collapse
|