Background
Commonly termed canker sores, aphthous ulcers, or aphthous stomatitis, have been the focus of study and research for many years, although the exact etiology of the lesions has yet to be identified. Categorized as an idiopathic disease, aphthous ulcers are frequently misdiagnosed, treated incorrectly, or simply ignored.
Recurrent aphthous ulcer (RAU), or recurrent aphthous stomatitis (RAS), represents a chronic inflammatory disease characterized by painful oral ulcers recurring with varying frequency. Examples of aphthous ulcers are shown in the images below.
Recurrent aphthae in floor of mouth, showing ovoid ulcer with inflammatory halo.
Typical aphthous ulcer in a common site, showing inflammatory halo surrounding a yellowish, round ulcer. Children with recurrent aphthous ulcers (canker sores) may reduce their oral food and fluid intake because of the associated pain and subsequently become dehydrated; therefore, aggressive therapy for the lesions can be important.
Recurrent aphthous ulcers (canker sores) may initially appear as erythematous, indurated papules that erode to form sharply circumscribed necrotic ulcers with a gray, fibrinous exudate and an erythematous halo. The 3 categories of recurrent aphthous ulcers (canker sores) are as follows:
- Minor aphthous ulcers (80-85% of recurrent aphthous ulcers [canker sores]) are 1-10 mm in diameter and heal spontaneously in 7-10 days.
- Major aphthous ulcers (also called Sutton disease) constitute 10-15% of recurrent aphthous ulcers (canker sores). These lesions are greater than 10 mm in diameter, take 10-30 days or more to heal, and may leave scars.
- Herpetiform ulcers (5-10% of recurrent aphthous ulcers [canker sores]) are multiple, clustered, 1-mm to 3-mm lesions that may coalesce into plaques. These usually heal in 7-10 days.
Pathophysiology
The pathophysiology of aphthous ulcers remains incompletely understood. The primary disorder appears to be the result of activation of the cell-mediated immune system. Early lesions show a cluster of macrophages and lymphocytes (predominantly cytotoxic and natural-killer T cells) at the preulcerative base, followed by formation of an ulcer with a neutrophilic base and an erythematous lymphocytic ring.
Patients with recurrent aphthous ulcers (canker sores) have increased numbers of cytotoxic CD8+ cells and decreased numbers of helper CD4+ cells in peripheral blood.[1] Lesions have elevated levels of interferon gamma, tumor necrosis factor-alpha, interleukin (IL)-2, IL-4, and IL-5;[2] they have a functional deficit of IL-10. Some lesions have also had mast-cell activation and degranulation. In vitro cytotoxicity to oral keratinocyte targets is greater in patients with active recurrent aphthous ulcers (canker sores) than in control subjects or in patients with traumatic ulcers. As expected with this abnormal immunologic activity, corticosteroids are effective therapy.
Aphthous ulcers may have abnormalities in cell communication and epithelial integrity. Lesions have increased expression of an adhesion molecule termed vascular cell adhesion molecule-1 (VCAM-1), E selectin, and keratinocyte intercellular adhesion molecule-1 (ICAM-1).[3] Connexins (markers for the presence of gap junctions) are present in the oral mucosa of patients with recurrent aphthous ulcers (canker sores) in amounts similar to those present in normal mucosal tissue. Experimental treatment with irsogladine maleate, which reinforces gap junctional intercellular communication, is effective. Helicobacter pylori may or may not be involved in aphthous ulcer formation.[4, 5]
Factors predisposing patients to recurrent aphthous ulcers (canker sores) may include trauma, emotional stress,[6, 7] poor nutritional status, thiamine deficiency,[8] vitamin B12 deficiency, malabsorption, celiac disease, regional enteropathy, menstruation, food hypersensitivity (eg, cow's milk),[9] allergic reaction, and exposure to toxins (eg, nitrates in drinking water). Aphthous ulcers (canker sores) are more prevalent in nonsmokers and in smokers who quit but are diminished with nicotine replacement therapy.
Epidemiology
Frequency
United States
Although recurrent aphthous ulcers (canker sores) are commonly believed to occur in approximately 20% of the general population, a study of medical and dental students revealed a prevalence of 31-66%.
International
The worldwide incidence is similar to that in the United States. Aphthous ulcers (canker sores) are found in all ethnic groups and geographic locations. The prevalence may be increased in affluent countries and socioeconomic classes.
Mortality/Morbidity
Aphthous ulcers (canker sores) are associated with local pain and discomfort. Symptoms usually last 2-10 days with minor and herpetiform ulcers and as long as 30 days with major ulcers. Most cases are self-limited and heal without sequelae in 7-14 days; however, major ulcers heal slowly (10-30 days or longer).
- Major aphthous ulcers (canker sores) have been known to leave substantial scars.
- The primary morbidity with any type of aphthous ulcer (canker sore) in the pediatric population is dehydration due to poor oral intake.
- Secondary bacterial infections are uncommon.
Race
Race does not appear to influence the frequency or severity of recurrent aphthous ulcers (canker sores).
Sex
Aphthous ulcers (canker sores) may be slightly more common in female individuals than in male individuals. Outbreaks occur most frequently during ovulation or before menstruation, and remissions are common during pregnancy.
Age
Recurrent aphthous ulcers (canker sores) begin in childhood or adolescence, with peak onset in persons aged 10-19 years. Frequency and severity diminish with age. Major aphthous ulcers (canker sores) may begin soon after puberty. Herpetiform recurrent aphthous ulcers (canker sores) tend to affect older persons.
Bachtiar EW, Cornain S, Siregar B, Raharjo TW. Decreased CD4+/CD8+ ratio in major type of recurrent aphthous ulcers: comparing major to minor types of ulcers. Asian Pac J Allergy Immunol. Jun-Sep 1998;16(2-3):75-9. [Medline].
Buno IJ, Huff JC, Weston WL, et al. Elevated levels of interferon gamma, tumor necrosis factor alpha, interleukins 2, 4, and 5, but not interleukin 10, are present in recurrent aphthous stomatitis. Arch Dermatol. Jul 1998;134(7):827-31. [Medline].
Healy CM, Thornhill MH. Induction of adhesion molecule expression on blood vessels and keratinocytes in recurrent oral ulceration. J Oral Pathol Med. Jan 1999;28(1):5-11. [Medline].
Birek C, Grandhi R, McNeill K, et al. Detection of Helicobacter pylori in oral aphthous ulcers. J Oral Pathol Med. May 1999;28(5):197-203. [Medline].
Maleki Z, Sayyari AA, Alavi K, Sayyari L, Baharvand M. A study of the relationship between Helicobacter pylori and recurrent aphthous stomatitis using a urea breath test. J Contemp Dent Pract. Jan 1 2009;10(1):9-16. [Medline].
Gallo Cde B, Mimura MA, Sugaya NN. Psychological stress and recurrent aphthous stomatitis. Clinics (Sao Paulo). 2009;64(7):645-8. [Medline].
Huling LB, Baccaglini L, Choquette L, Feinn RS, Lalla RV. Effect of stressful life events on the onset and duration of recurrent aphthous stomatitis. J Oral Pathol Med. Feb 2012;41(2):149-52. [Medline].
Haisraeli-Shalish M, Livneh A, Katz J, et al. Recurrent aphthous stomatitis and thiamine deficiency. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. Dec 1996;82(6):634-6. [Medline].
Besu I, Jankovic L, Magdu IU, Konic-Ristic A, Raskovic S, Juranic Z. Humoral immunity to cow's milk proteins and gliadin within the etiology of recurrent aphthous ulcers?. Oral Dis. Nov 2009;15(8):560-4. [Medline].
Thomas KT, Feder HM Jr, Lawton AR, Edwards KM. Periodic fever syndrome in children. J Pediatr. Jul 1999;135(1):15-21. [Medline].
Padeh S, Brezniak N, Zemer D, et al. Periodic fever, aphthous stomatitis, pharyngitis, and adenopathy syndrome: clinical characteristics and outcome. J Pediatr. Jul 1999;135(1):98-101. [Medline].
Ghodratnama F, Wray D, Bagg J. Detection of serum antibodies against cytomegalovirus, varicella zoster virus and human herpesvirus 6 in patients with recurrent aphthous stomatitis. J Oral Pathol Med. Jan 1999;28(1):12-5. [Medline].
Lin SS, Chou MY, Ho CC, et al. Study of the viral infections and cytokines associated with recurrent aphthous ulceration. Microbes Infect. Apr 2005;7(4):635-44. [Medline].
Arikan S, Durusoy C, Akalin N, Haberal A, Seckin D. Oxidant/antioxidant status in recurrent aphthous stomatitis. Oral Dis. Oct 2009;15(7):512-5. [Medline].
Gupta SK, Gupta RC, Seth AK, et al. Epidemiological evaluation of recurrent stomatitis, nitrates in drinking water, and cytochrome b5 reductase activity. Am J Gastroenterol. Jul 1999;94(7):1808-12. [Medline].
Herlofson BB, Barkvoll P. Sodium lauryl sulfate and recurrent aphthous ulcers. A preliminary study. Acta Odontol Scand. Oct 1994;52(5):257-9. [Medline].
Herlofson BB, Barkvoll P. The effect of two toothpaste detergents on the frequency of recurrent aphthous ulcers. Acta Odontol Scand. Jun 1996;54(3):150-3. [Medline].
Hasan AA, Ciancio S. Association between ingestion of nonsteroidal anti-inflammatory drugs and the emergence of aphthous-like ulcers. J Int Acad Periodontol. Jan 2009;11(1):155-9. [Medline].
Koridze Kh. Definition of risk of the aphthous stomatitis by hygienic indices [in Russian]. Georgian Med News. Apr 2005;25-8. [Medline].
Ficarra G. Oral ulcers in HIV-infected patients: an update on epidemiology and diagnosis. Oral Dis. May 1997;3 Suppl 1:S183-9. [Medline].
Liu C, Zhou Z, Liu G, Wang Q, Chen J, Wang L. Efficacy and safety of dexamethasone ointment on recurrent aphthous ulceration. Am J Med. Mar 2012;125(3):292-301. [Medline].
Vincent SD, Lilly GE. Clinical, historic, and therapeutic features of aphthous stomatitis. Literature review and open clinical trial employing steroids. Oral Surg Oral Med Oral Pathol. Jul 1992;74(1):79-86. [Medline].
Holbrook WP, Kristmundsdottir T, Loftsson T. Aqueous hydrocortisone mouthwash solution: clinical evaluation. Acta Odontol Scand. Jun 1998;56(3):157-60. [Medline].
Pakfetrat A, Mansourian A, Momen-Heravi F, Delavarian Z, Momen-Beitollahi J, Khalilzadeh O, et al. Comparison of colchicine versus prednisolone in recurrent aphthous stomatitis: A double-blind randomized clinical trial. Clin Invest Med. Jun 1 2010;33(3):E189-95. [Medline].
Bell J. Amlexanox for the treatment of recurrent aphthous ulcers. Clin Drug Investig. 2005;25(9):555-66. [Medline].
Binnie WH, Curro FA, Khandwala A, Van Inwegan RG. Amlexanox oral paste: a novel treatment that accelerates the healing of aphthous ulcers. Compend Contin Educ Dent. Nov 1997;18(11):1116-8, 1120-2, 1124 passim. [Medline].
Greer RO Jr, Lindenmuth JE, Juarez T, Khandwala A. A double-blind study of topically applied 5% amlexanox in the treatment of aphthous ulcers. J Oral Maxillofac Surg. Mar 1993;51(3):243-8; discussion 248-9. [Medline].
Khandwala A, Van Inwegen RG, Alfano MC. 5% amlexanox oral paste, a new treatment for recurrent minor aphthous ulcers: I. Clinical demonstration of acceleration of healing and resolution of pain. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. Feb 1997;83(2):222-30. [Medline].
Murray B, McGuinness N, Biagioni P, et al. A comparative study of the efficacy of Aphtheal in the management of recurrent minor aphthous ulceration. J Oral Pathol Med. Aug 2005;34(7):413-9. [Medline].
Gorsky M, Epstein J, Raviv A, Yaniv R, Truelove E. Topical minocycline for managing symptoms of recurrent aphthous stomatitis. Spec Care Dentist. Jan-Feb 2008;28(1):27-31. [Medline].
Skulason S, Holbrook WP, Kristmundsdottir T. Clinical assessment of the effect of a matrix metalloproteinase inhibitor on aphthous ulcers. Acta Odontol Scand. Feb 2009;67(1):25-9. [Medline].
Gorsky M, Epstein J, Rabenstein S, Elishoov H, Yarom N. Topical minocycline and tetracycline rinses in treatment of recurrent aphthous stomatitis: a randomized cross-over study. Dermatol Online J. 2007;13(2):1. [Medline].
Rattan J, Schneider M, Arber N, et al. Sucralfate suspension as a treatment of recurrent aphthous stomatitis. J Intern Med. Sep 1994;236(3):341-3. [Medline].
Jasmin JR, Muller-Giamarchi M, Jonesco-Benaiche N. Local treatment of minor aphthous ulceration in children. ASDC J Dent Child. Jan-Feb 1993;60(1):26-8. [Medline].
Kutcher M. Evaluating the efficacy of 2-octyl cyanoacrylate bioadhesive for treatment of oral ulcerations. Compend Contin Educ Dent Suppl. 2001;12-6; quiz 22. [Medline].
Kutcher MJ, Ludlow JB, Samuelson AD, Campbell T, Pusek SN. Evaluation of a bioadhesive device for the management of aphthous ulcers. J Am Dent Assoc. Mar 2001;132(3):368-76. [Medline].
Shemer A, Amichai B, Trau H, Nathansohn N, Mizrahi B, Domb AJ. Efficacy of a mucoadhesive patch compared with an oral solution for treatment of aphthous stomatitis. Drugs R D. 2008;9(1):29-35. [Medline].
Mizrahi B, Golenser J, Wolnerman JS, Domb AJ. Adhesive tablet effective for treating canker sores in humans. J Pharm Sci. Dec 2004;93(12):2927-35. [Medline].
Rhodus NL, Bereuter J. An evaluation of a chemical cautery agent and an anti-inflammatory ointment for the treatment of recurrent aphthous stomatitis: a pilot study. Quintessence Int. Dec 1998;29(12):769-73. [Medline].
Porter SR, Al-Johani K, Fedele S, Moles DR. Randomised controlled trial of the efficacy of HybenX in the symptomatic treatment of recurrent aphthous stomatitis. Oral Dis. Mar 2009;15(2):155-61. [Medline].
Moghadamnia AA, Motallebnejad M, Khanian M. The efficacy of the bioadhesive patches containing licorice extract in the management of recurrent aphthous stomatitis. Phytother Res. Feb 2009;23(2):246-50. [Medline].
Burgess JA, van der Ven PF, Martin M, Sherman J, Haley J. Review of over-the-counter treatments for aphthous ulceration and results from use of a dissolving oral patch containing glycyrrhiza complex herbal extract. J Contemp Dent Pract. Mar 1 2008;9(3):88-98. [Medline].
Martin MD, Sherman J, van der Ven P, Burgess J. A controlled trial of a dissolving oral patch concerning glycyrrhiza (licorice) herbal extract for the treatment of aphthous ulcers. Gen Dent. Mar-Apr 2008;56(2):206-10; quiz 211-2, 224. [Medline].
Buchsel PC. Polyvinylpyrrolidone-sodium hyaluronate gel (Gelclair): a bioadherent oral gel for the treatment of oral mucositis and other painful oral lesions. Expert Opin Drug Metab Toxicol. Nov 2008;4(11):1449-54. [Medline].
Katz J, Langevitz P, Shemer J, et al. Prevention of recurrent aphthous stomatitis with colchicine: an open trial. J Am Acad Dermatol. Sep 1994;31(3 Pt 1):459-61. [Medline].
Mimura MA, Hirota SK, Sugaya NN, Sanches Jr JA, Migliari DA. Systemic treatment in severe cases of recurrent aphthous stomatitis: an open trial. Clinics (Sao Paulo). 2009;64(3):193-8. [Medline].
de Abreu MA, Hirata CH, Pimentel DR, Weckx LL. Treatment of recurrent aphthous stomatitis with clofazimine. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. Nov 2009;108(5):714-21. [Medline].
Revuz J, Guillaume JC, Janier M, et al. Crossover study of thalidomide vs placebo in severe recurrent aphthous stomatitis. Arch Dermatol. Jul 1990;126(7):923-7. [Medline].
Jacobson JM, Greenspan JS, Spritzler J, et al. Thalidomide for the treatment of oral aphthous ulcers in patients with human immunodeficiency virus infection. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. N Engl J Med. May 22 1997;336(21):1487-93. [Medline].
Wu JJ, Huang DB, Pang KR, et al. Thalidomide: dermatological indications, mechanisms of action and side-effects. Br J Dermatol. Aug 2005;153(2):254-73. [Medline].
Altenburg A, Zouboulis CC. Current concepts in the treatment of recurrent aphthous stomatitis. Skin Therapy Lett. Sep 2008;13(7):1-4. [Medline].
O'Neill ID. Off-label use of biologicals in the management of inflammatory oral mucosal disease. J Oral Pathol Med. Nov 2008;37(10):575-81. [Medline].
Tezel A, Kara C, Balkaya V, Orbak R. An Evaluation of Different Treatments for Recurrent Aphthous Stomatitis and Patient Perceptions: Nd:YAG Laser versus Medication. Photomed Laser Surg. Feb 2009;27(1):101-6. [Medline].
Zand N, Ataie-Fashtami L, Djavid GE, Fateh M, Alinaghizadeh MR, Fatemi SM, et al. Relieving pain in minor aphthous stomatitis by a single session of non-thermal carbon dioxide laser irradiation. Lasers Med Sci. Apr 12 2008;[Medline].
Sharon-Buller A, Sela M. CO2-laser treatment of ulcerative lesions. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. Mar 2004;97(3):332-4. [Medline].
De Souza TO, Martins MA, Bussadori SK, Fernandes KP, Tanji EY, Mesquita-Ferrari RA, et al. Clinical evaluation of low-level laser treatment for recurring aphthous stomatitis. Photomed Laser Surg. Oct 2010;28 Suppl 2:S85-8. [Medline].
Alidaee MR, Taheri A, Mansoori P, Ghodsi SZ. Silver nitrate cautery in aphthous stomatitis: a randomized controlled trial. Br J Dermatol. Sep 2005;153(3):521-5. [Medline].
Volkov I, Rudoy I, Freud T, et al. Effectiveness of vitamin B12 in treating recurrent aphthous stomatitis: a randomized, double-blind, placebo-controlled trial. J Am Board Fam Med. Jan-Feb 2009;22(1):9-16. [Medline].
Gulcan E, Toker S, Hatipoglu H, Gulcan A, Toker A. Cyanocobalamin may be beneficial in the treatment of recurrent aphthous ulcers even when vitamin B12 levels are normal. Am J Med Sci. Nov 2008;336(5):379-82. [Medline].
Carrozzo M. Vitamin B12 for the treatment of recurrent aphthous stomatitis. Evid Based Dent. 2009;10(4):114-5. [Medline].
Yasui K, Kurata T, Yashiro M, Tsuge M, Ohtsuki S, Morishima T. The effect of ascorbate on minor recurrent aphthous stomatitis. Acta Paediatr. Mar 2010;99(3):442-5. [Medline].
Wright EF. Clinical effectiveness of lysine in treating recurrent aphthous ulcers and herpes labialis. Gen Dent. Jan-Feb 1994;42(1):40-2; quiz 51-2. [Medline].
Zhou Y, Chen Q, Meng W, Jiang L, Wang Z, Liu J, et al. Evaluation of penicillin G potassium troches in the treatment of minor recurrent aphthous ulceration in a Chinese cohort: a randomized, double-blinded, placebo and no-treatment-controlled, multicenter clinical trial. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. Apr 2010;109(4):561-6. [Medline].
Hamdy AA, Ibrahem MA. Management of aphthous ulceration with topical quercetin: a randomized clinical trial. J Contemp Dent Pract. 2010;11(4):E009-16. [Medline].
Samet N, Laurent C, Susarla SM, Samet-Rubinsteen N. The effect of bee propolis on recurrent aphthous stomatitis: a pilot study. Clin Oral Investig. Jun 2007;11(2):143-7. [Medline].
Shrivastava R, John GW. Treatment of Aphthous Stomatitis with topical Alchemilla vulgaris in glycerine. Clin Drug Investig. 2006;26(10):567-73.
Thornhill MH, Baccaglini L, Theaker E, Pemberton MN. A randomized, double-blind, placebo-controlled trial of pentoxifylline for the treatment of recurrent aphthous stomatitis. Arch Dermatol. Apr 2007;143(4):463-70. [Medline].
Yang TY, Jang TY. The value of local botulinum toxin A injection in the treatment of the pain of aphthous ulcer. Eur Arch Otorhinolaryngol. Mar 2009;266(3):445-8. [Medline].
Collier PM, Neill SM, Copeman PW. Topical 5-aminosalicylic acid: a treatment for aphthous ulcers. Br J Dermatol. Feb 1992;126(2):185-8. [Medline].
Sharquie KE, Najim RA, Al-Hayani RK, Al-Nuaimy AA, Maroof DM. The therapeutic and prophylactic role of oral zinc sulfate in management of recurrent aphthous stomatitis (ras) in comparison with dapsone. Saudi Med J. May 2008;29(5):734-8. [Medline].
Hunter IP, Ferguson MM, Scully C, et al. Effects of dietary gluten elimination in patients with recurrent minor aphthous stomatitis and no detectable gluten enteropathy. Oral Surg Oral Med Oral Pathol. May 1993;75(5):595-8. [Medline].
Brice SL. Clinical evaluation of the use of low-intensity ultrasound in the treatment of recurrent aphthous stomatitis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. Jan 1997;83(1):14-20. [Medline].
Skaare AB, Herlofson BB, Barkvoll P. Mouthrinses containing triclosan reduce the incidence of recurrent aphthous ulcers (RAU). J Clin Periodontol. Aug 1996;23(8):778-81. [Medline].
Fridh G, Koch G. Effect of a mouth rinse containing amyloglucosidase and glucose oxidase on recurrent aphthous ulcers in children and adolescents. Swed Dent J. 1999;23(2-3):49-57. [Medline].
Field EA, Brookes V, Tyldesley WR. Recurrent aphthous ulceration in children--a review. Int J Paediatr Dent. Apr 1992;2(1):1-10. [Medline].
Hodosh M, Hodosh SH, Hodosh AJ. Treatment of aphthous stomatitis with saturated potassium nitrate/dimethyl isosorbide. Quintessence Int. Feb 2004;35(2):137-41. [Medline].
Mahdi AB, Coulter WA, Woolfson AD, Lamey PJ. Efficacy of bioadhesive patches in the treatment of recurrent aphthous stomatitis. J Oral Pathol Med. Sep 1996;25(8):416-9. [Medline].
Rogers RS. Recurrent aphthous stomatitis: clinical characteristics and associated systemic disorders. Semin Cutan Med Surg. Dec 1997;16(4):278-83. [Medline].
Saxen MA, Ambrosius WT, Rehemtula al-KF AL, et al. Sustained relief of oral aphthous ulcer pain from topical diclofenac in hyaluronan: a randomized, double-blind clinical trial. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. Oct 1997;84(4):356-61. [Medline].
Scully C. Clinical practice. Aphthous ulceration. N Engl J Med. Jul 13 2006;355(2):165-72. [Medline].
Ueta E, Osaki T, Yoneda K, et al. A clinical trial of Azelastine in recurrent aphthous ulceration, with an analysis of its actions on leukocytes. J Oral Pathol Med. Mar 1994;23(3):123-9. [Medline].
Victoria JM, Correia-Silva Jde F, Pimenta FJ, et al. Serotonin transporter gene polymorphism (5-HTTLPR) in patients with recurrent aphthous stomatitis. J Oral Pathol Med. Sep 2005;34(8):494-7. [Medline].
Wormser GP, Mack L, Lenox T, et al. Lack of effect of oral acyclovir on prevention of aphthous stomatitis. Otolaryngol Head Neck Surg. Jan 1988;98(1):14-7. [Medline].
Ylikontiola L, Sorsa T, Hayrinen-Immonen R, Salo T. Doxymycine-cyanoacrylate treatment of recurrent aphthous ulcers. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. Mar 1997;83(3):329-33. [Medline].

