oral side effects after covid vaccine

There were no life-threatening reactions. 2022 Oct;11(10):5879-5886. doi: 10.4103/jfmpc.jfmpc_205_22. 2020;71(8):193742. The Sputnik V vaccine also uses Ad26. 2021;21(2):18192. Oral side effects of COVID-19 vaccine - PubMed Guillain-Barr syndrome (GBS). https://doi.org/10.1161/CIRCULATIONAHA.121.055891. This Surprising Side Effect Shows Up Months After COVID 406 were considered non-serious (0.005% of bivalent COVID-19 doses administered) and 112 (0.0014% of bivalent COVID-19 doses administered) were considered serious. Taylor PC, Adams AC, Hufford MM, de la Torre I, et al. J Family Med Prim Care. For the Pfizer vaccine, myocarditis was most common during the 7days after the second Pfizer-BioNTech dose for males and females aged 1617, at 105.86 [95% CI, 91.65122.27] and 10.98 [95% CI, 7.1616.84] cases per million doses, respectively. Sputnik Light can be stored at 28C, compared to Sputnik V, which must be stored at below 18C. 4 The most common systemic adverse event was fatigue (546 [8.2%] participants in the vaccine group and 248 [7.0%] in placebo group). https://doi.org/10.1056/NEJMoa2107934. The CDC's guidance on common vaccine side effects lists many of the same ones Chambers mentioned: fever, chills, headaches, nausea, and muscle pain or exhaustion. 2022;386(22):2097111. Radiology. Mounting evidence suggests Sputnik COVID vaccine is safe and effective. Clinical characteristics and outcomes of coronavirus disease 2019 patients who received compassionate-use leronlimab. 2021;325(15):15351544. Hence, the aim of this study was to compare the orofacial adverse effects of two recently authorised COVID-19 vaccines, namely BNT162b2 and mRNA-1273. Also, if possible, get some rest. In the absence of direct evidence, we expect drugs of a similar class to have similar toxicity. Body pains, mouth ulcers experienced by some healthcare workers after Of 151 healthy volunteers who received the SCB-2019 vaccine almost half reported local site reactions, more frequent with the AS03 adjuvant (4469%) than the CpG/Alum adjuvant (644%) or no adjuvant (313%). Oral Side Effects [ Time Frame: 0-30 days after the COVID-19 vaccine shot ] Dichotomous outcome for the emergence of oral side effects (e.g. The majority of Americans who have not been vaccinated or who say they are hesitant about vaccinating their children report that safety is their main concern. Disclaimer. Why Some People Suffer Severe Side Effects After COVID-19 Vaccines Bozkurt et al. Would you like email updates of new search results? The common side effects for the Moderna and Pfizer-BioNTech Covid vaccines include things like pain and swelling on your arm where you get the shot, and flu-like symptoms including fatigue, headache, fever and chills. They found that six of 21 COVID-19 patients who had external skin rashes also had oral lesions. https://doi.org/10.1038/s41415-021-2615-x, DOI: https://doi.org/10.1038/s41415-021-2615-x. HHS Vulnerability Disclosure, Help Possible adverse effects to mRNA vaccines include the generation of autoantibodies, adverse reactions to adjuvants, or diluents, and induction of type I interferon responses. But reactions can vary wildly, and they don't reflect how your immune system would respond to a COVID-19 infection. https://doi.org/10.1002/jcph.1693. Vxart's Covid vaccine is in a small tablet and can be shipped and stored at room temperature, unlike Pfizer and Moderna's vaccines. The chances of any of these side effects occurring after vaccination differ according to the specific vaccine. This site needs JavaScript to work properly. Publicly available data on BNT162b2 and mRNA-1273 vaccines were accessed from the relevant regulatory authorities in the United States, Canada, European Union and United Kingdom. Post-vaccine side effects can include soreness at the site of injection, a low-grade fever, headaches, muscle aches and fatigue, Moss said. 2022;399(10323):46172. Serious events were reported in 0.6% of patients in the vaccine group and 0.5% in the placebo group, most frequently appendicitis (7 vs 2 cases), acute myocardial infarction (3 vs 0 cases) and cerebrovascular accident (3 cases vs 1 case). 2022 Mar 1;60(2):224-228. COVID-19: Vaccine side effects and reactions - Ministry of Health NZ https://doi.org/10.1056/NEJMoa2104840. FDA grants Dupixent (dupilumab) Breakthrough Therapy designation for But the rare side effects identified with COVID vaccines have to be weighed against the known, higher risks from contracting COVID, Goepfert says. 2021 May 7;18(9):4965. doi: 10.3390/ijerph18094965. It is administered to patients who have contracted the disease and are at high risk for deterioration without intervention. FOIA Efforts to develop therapeutics have led to innovations such as mRNA vaccines and oral antivirals. Another study compared the efficacy of sotrovimab in 546 hospitalized patients with SARS-CoV-2 to 0.9% saline and used the composite endpoint of length-of-stay and recurrent admissions and reported infusion-related adverse events in 18 patients (10%) who received sotrovimab and 14 patients (13%) who received saline. Cytokine storm refers to fevers, chills, myalgias, and acute lung injury resulting from direct activation of various immunocompetent cells including macrophages, monocytes, lymphocytes, and natural killers (NK) cells. The most common side effects . The clots linked to the vaccine were a dangerous type in the brain, while birth control pills increase the chances of a blood clot in the leg or lung a point quickly noted by many experts. editors. Descotes J. Immunotoxicity of monoclonal antibodies. An analysis of self-reports from 3236 Iranian healthcare workers in Mazandaran, Iran, who were vaccinated with Sputnik V (mean age 39.32, 61.2% women) reported pain (56.9%), fatigue (50.9%), body pain (43.9%), headache (35.7%), fever (32.9%), joint pain (30.3%), chills (29.8%), and drowsiness (20.3%) as the most common side effects [114]. More unusual effects such as anaphylaxis and blood clots. 2015;15(2):517. Kishimoto T. Interleukin-6: from basic science to medicine40 years in immunology. Avoid the most common mistakes and prepare your manuscript for journal Sotrovimab binds to the S2 subunit [16]. mRNA vaccines are not infectious and carry no risk of insertional mutagenesis [58]. Cases of TTS were reported in individuals who received the Oxford-AstraZeneca vaccine (ChAdOx1 nCoV-19) 516days earlier. 1953;98(6):64156. 2020;72(4):11691176. 2021;25(3):16631669. Rosner CM, Genovese L, Tehrani BN, Atkins M, et al. 2022 Dec;114(6):601-612. doi: 10.1016/j.jnma.2022.08.003. Sawires L. Effects of the influenza vaccine on the oral cavity. The FDA authorized dose for the combination for adults is bamlanivimab 700mg and etesevimab 1400mg, not the 2800mg and 2800mg used in the studies discussed above. That's because the first dose triggers an immune response, and the second dose "boosts" it. Luyten J, Bruyneel L, van Hoek A J. Assessing vaccine hesitancy in the UK population using a generalized vaccine hesitancy survey instrument. SARS-CoV-2 Neutralizing antibody LY-CoV555 in outpatients with Covid-19. https://www.cdc.gov/vaccines/covid-19/clinical-considerations/myocarditis.html. The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis. The authors assessed gender based on the gender listed in each users profile. N Engl J Med. 2020;16(3):28494. Most cases (67%) occurred in males. There have been no reports of thromboembolic events from Russian health authorities or from those other nations using Sputnik V [116]. Both vaccines deliver mRNA encoding the entire S protein with 2 equal proline substitutions for stability. Tang CH, Hsu CJ, Fong YC. News and information by and for the UAB community, "Many people worry that these vaccines were rushed into use and still do not have full FDA approval they are currently being distributed under Emergency Use Authorizations. Individuals who receive a bivalent COVID-19 vaccine may experience side effects commonly reported by individuals who receive authorized or approved monovalent mRNA COVID-19 vaccines.. Use or keep moving your arm. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. Blumenthal KG, Robinson LB, Camargo CA Jr, Shenoy ES, Banerji A, et al. https://doi.org/10.1126/sciimmunol.aaf7643, Stephenson KE, Le Gars M, Sadoff J, de Groot AM, et al. COVID-19 vaccine side effects reported by women more than - ABC News CDC: Safe to take Tylenol or OTC pain medications after Covid vaccine This Vaccine Side Effect Could Mean You Already Had COVID, New - Yahoo! VERIFY: Are there long-term side effects from the COVID vaccines? The most common side effects following COVID-19 vaccines are fatigue, a fever, headaches, body aches, chills, nausea, diarrhea, and pain at the site of injection, according to the World. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Vaxart said the vaccine generated a type of T-cell responsible . -, Tarakji B, Umair A, Alakeel R et al. Perhaps the antibodies the immune system makes have off-target effects (molecular mimicry). They then resolve quickly. One of the most unusual and serious side-effects of the COVID-19 vaccine jab, which has been reported from various corners is Blood clotting. The certification, normally $1,500, is $650 for students and $750 for nonstudents. Further complicating comparison, Moderna was authorized later than Pfizer leading to possible confounding by the varying inflammatory effects of different SARS-CoV-2 variants. Absent new data, we reiterate the general observation that toxicity from recombinant proteins results from inadvertently activating the immune system and off-target binding, which may manifest as type II or III hypersensitivity. COVID-19 vaccine safety updates: primary series in children and adolescents ages 511 and 1215 years, and booster doses in adolescents ages 1624 years. Oster ME, Shay DK, Su JR, Gee J, et al. We dont know why that is, how long these symptoms will last or if there are effective ways to treat them. Monoclonal antibodies prevent progression to severe disease, are not equally effective across variants, and are associated with minimal and self-limited reactions. Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial. These side effects are normal and signs that your immune system is building protection against the virus. Accessed 23 Mar 2022, U.S. Food and Drug Administration. MMWR Morb Mortal Wkly Rep. 2021;70(2):4651. https://doi.org/10.1161/CIRCULATIONAHA.121.056135. Health Canada and PHAC review the reports to determine whether the vaccine may have played a role. Immune Netw. https://doi.org/10.1056/NEJMoa2029849. Association of myocarditis with BNT162b2 messenger RNA COVID-19 vaccine in a case series of children. The most reported symptoms after the first and second doses were pain at the injection site (83.7% and 88.7%, respectively), fatigue (37.2% and 65.2%), headache (32.7% and 58.5%), muscle pain (22.7% and 57.6%), and arthralgia (16.6% and 42.6%) [65]. Parasitism - Wikipedia However, according to the data, a tiny. Others could be more systemic, such as low-grade fever, achiness, or fatigue that ranges from mild to severe. Su JR. Recent advances of vaccine adjuvants for infectious diseases. In the Pfizer-BioNTech vaccine trials, more than 77% of participants reported at least one systemic reaction. This paper, along with its companion that covers xenobiotics and alternative remedies, is an update to . Oral side effects of COVID-19 vaccine. 1;5(4):e227038. There should be confidence in that.. Cetuximab, an anti-EGFR monoclonal antibody used to treat head and neck cancer illustrates adverse effects from off-target binding. 2021;595(7867):33940. But as Professor Diane Tucker, Ph.D., explains, you can take control and make the most of this historic opportunity. After the EUA, bamlanivimab 700mg and etesevimab 1400mg have been administered to roughly 800 patients across all clinical trials. volume230,page 59 (2021)Cite this article. Accessed 26 Feb 2022 from https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2022-01-05/02-covid-su-508.pdf. Reactions that occurred within 24h of the infusion were considered related to the infusion. White spots on your tongue can be a sign of Covid or a vaccine side effect, says expert WHITE spots on the tongue - it's usually nothing serious. Accessed 22 Mar 2022, National Center for Immunization and Respiratory Diseases (U.S.).Division of Viral Diseases, Moderna COVID-19 Vaccine (also known as Spikevax) Overview and Safety. Dionne A, Sperotto F, Chamberlain S, Baker AL, et al. Pfizer-BioNTech (BNT162b2), Moderna (mRNA-1273) COVID-19 mRNA vaccines and hypersensitivity reactions. 8600 Rockville Pike Hepatitis B vaccination and associated oral manifestations: A non-systematic review of literature and case reports. Up to 10 percent of people who have COVID experience side effects such as difficulty thinking, pain, tiredness, loss of taste and depression. Data in December 2020 estimated the incidence of anaphylaxis to the first dose of the Pfizer-BioNTech vaccine as 4.7 cases per 1,000,000 doses [78]. 2021;6:99. https://doi.org/10.1038/s41578-021-00281-4. Vaccines are just designed to deliver a payload and then are quickly eliminated by the body, Goepfert said. https://doi.org/10.1093/cid/ciaa449. Davenport FM, Hennessy AV, Francis T Jr. Epidemiologic and immunologic significance of age distribution of antibody to antigenic variants of influenza virus. To date, vaccines have focused on raising immunity against the S protein, the protein SARS-CoV-2 uses to attach to and enter host cells. -. The following outcomes were selected and defined by the authors based on information from regulatory authorities, previous studies, large-scale adverse events initiatives: febrile seizure, aseptic. https://doi.org/10.15585/mmwr.mm7035e5. In 1999, a vaccine against rotavirus, which can cause life-threatening diarrhea in infants, was pulled from the market after more than a dozen cases of bowel obstruction were reported in the first six months of use. Your IP: Four patients with SARS-CoV-2 on mechanical ventilation and vasopressors were able to be extubated and weaned off pressors after receiving two infusions of 700mg leronlimab two weeks apart and IL-6 levels decreased, but these patients also received hydroxychloroquine, zinc, tocilizumab, remdesivir, and azithromycin [20]. Bamlanivimab/etesevimab is given as an IV infusion in 0.9% saline. 2021;144(6):5025. Published by John Wiley & Sons Ltd. Here's what you should know. Sci Rep. 2021;11(1):21464. https://doi.org/10.1038/s41598-021-00963-7. "Delayed dermal events with both hyaluronic acid and non-hyaluronic acid fillers have . Hum Vaccin Immunother. Larocca RA, Provine NM, Aid M, Iampietro MJ, et al. The median age was 10years (IQR, 911years). To date, no clinical trials have been performed. 2010;62(12):361524. Ad26 elicits a less robust T cell response than Ad5 [109] but escapes immunity to Ad5 [110]. In rare cases, coronavirus vaccines may cause Long Covid - Science In 1976, a vaccine against swine flu that was widely distributed in the United States was identified in rare cases (approximatelyone in 100,000) as a cause of Guillain-Barr Syndrome, in which the immune system attacks the nerves. U.S. Food and Drug Administration. Established by a committee of individuals from across the university and UAB Medicine, Wellness Week is designed to help the UAB community prioritize rest, well-being, mindfulness, movement and good nutrition. Embolic and thrombotic events occurred at a frequency of 0.06% in the vaccine group and 0.05% in the placebo group. Cloudflare Ray ID: 7a2b87bd69212d04 COVID-19 vaccine safety: Summary of weekly report on side effects JAMA. You need 2 doses for stronger and longer-lasting protection. Accessed 26 Feb 2022. The most common side effects of the COVID-19 vaccines include: redness, pain, or. 2021;326(1):3545. Each Wednesday in October, join Walk with Wellness meetings on the UAB Walking Trails. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Pfizer and Moderna and later Johnson & Johnson and then Novavax, which reported on its Phase III trial results in June 2021 "all have enrolled 30,000-plus individuals, half of whom got the vaccine and half of whom got a placebo initially, after which all the placebo group got the vaccine," Goepfert said. https://doi.org/10.1056/NEJMoa2109730. This narrative review describes the effects of vaccines and monoclonal antibodies that a clinician is likely to encounter when treating patients affected by COVID-19. Activate your accountandexplore new ways to earn cash rewards. Nat Rev Immunol. The highest incidence occurred in those ages 30 to 39 (10.6 cases per million vaccine doses), followed by those 40 to 49years of age (9.0 cases per million vaccine doses). Drinking lots of fluids is wise if you're feverish, and wearing lightweight clothing can also keep you comfortable. Circulation. More recently, an even more rare side effect myocarditis, or inflammation of the heart muscle has beenreported in peoplereceiving Pfizer and Moderna COVID-19 vaccines. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Khubchandani J, Sharma S, Price JH, Wiblishauser MJ, et al. Accessed 18 Jan 2022, U.S. Food and Drug Administration. 2022 Jan;22(1):64-72. doi: 10.1016/S1473-3099(21)00451-5. We thank the administrative staff at Boston Childrens Hospital and Weill Cornell Medicine for their support. Plasma exchange can be used in those who do not respond to IVIG. Throughout Wellness Week Oct. 17-21, employees and students from across UAB and UAB Medicine shared dozens of photos and videos that represent what wellness means to them. Granados Villalpando JM, Romero Tapia SJ, Baeza Flores GDC, Ble Castillo JL, Juarez Rojop IE, Lopez Junco FI, Olvera Hernndez V, Quiroz Gomez S, Ruiz Quiones JA, Guzmn Priego CG. Bethesda, MD 20894, Web Policies Circulation. Even as cases, hospitalizations and deaths have declined significantly in Alabama since January, there are still nearly 250 new COVID cases diagnosed and nearly 10 deaths reported statewide per day as of mid-June. Fischer S, Cabrera-Fuentes HA, Noll T, Preissner KT. Macchia A, Ferrante D, Angeleri P, Biscayart C, et al. Voleti N, Reddy SP, Ssentongo P. Myocarditis in SARS-CoV-2 infection vs. COVID-19 vaccination: a systematic review and meta-analysis. Binding to the RBD prevents SARS-CoV-2 from attaching to and then infecting human cells. She says . These results have already sparked several new programs and initiatives; anyone can contribute ideas and perspectives following a second seminar Nov. 16. In clinical trials, Moderna's vaccine reported 94.1% effectiveness at preventing COVID-19 in people who received both doses. J Natl Med Assoc. Both patient/recipient information and healthcare professional fact sheets for each of these drugs were manually searched to find their orofacial adverse effects. 2021;4:100083. https://doi.org/10.1016/j.jtauto.2021.100083. The mum-of-two, from Tysoe, Stratford-upon-Avon, went to her GP after finding a lump but was told there was "nothing to worry about" and it might've been a side effect of her Covid vaccine. Chary MA, Barbuto AF, Izadmehr S, Hayes BD, Burns MM. It is not clear how COVID variants such as the highly infectious Delta mutation may affect patients. PMC All symptoms resolved after medical treatment without sequelae. Bookshelf https://doi.org/10.15585/mmwr.mm7004e1. Effect of bamlanivimab as monotherapy or in combination with etesevimab on viral load in patients with mild to moderate COVID-19: a randomized clinical trial. A person might also experience side effects around the injection site, which is usually the upper arm. "Up to 10 percent of people who have COVID experience side effects such as difficulty thinking, pain, tiredness, loss of taste and depression. Epub 2021 Aug 16. https://doi.org/10.1136/bmj.n912. Covid vaccine: Vaxart shares plunge on weak antibody response to oral https://doi.org/10.1038/d41586-021-02796-w. Baraniuk C. What do we know about Chinas covid-19 vaccines? For comparison, incidence of anaphylaxis to succinylcholine, vancomycin, and piperacillin/tazobactam have been estimated at 1.11, 0.57, and 0.35 per 1,000,000 administrations, respectively [90]. There should be confidence in that. By Linda. Possible Side Effects After Getting a COVID-19 Vaccine | CDC Vaccines (Basel). Weekly meetings of the Grief Recovery Method Support Group will begin Feb. 20. Google Scholar. People react differently after being vaccinated. Steroids, some prescription drugs may reduce COVID-19 vaccine efficacy JAMA. JAMA. The second dose, given 3weeks later, uses Ad26. J Control Release. The FDA cite an interim unpublished analysis for the lower dose. The Johnson & Johnson COVID-19 Vaccine (Ad26.COV2.S) is the third vaccine to receive EUA by the FDA for the prevention of COVID-19 in patients 18years of age and older [49]. Take a walk around campus to find a little-known green space closest to you and take a moment for mindfulness using this Google Map we created just for you. Hepatitis B vaccination and associated oral manifestations: A non-systematic review of literature and case reports. University of Florida, 2018. The estimated incidence of anaphylaxis to the first dose of the Moderna vaccine was 2.5 per 1,000,000 doses. Sotrovimab binds to a region in S2 that helps the host and virus membrane fuse. 2021;6(10):12026. These might include swelling, pain, redness, an itchy rash, and other mild forms of . https://doi.org/10.1136/heartjnl-2020-317056. The S protein is composed of a region that attaches to the ACE2 receptor (the receptor binding domain (RBD) or S1) and a region that facilitates fusion of the host and virus membranes (S2) [6]. Ten (7%) of 143 participants in phase 1 had a clinically significant increase of laboratory indicators (transaminase elevations, CK elevation, or blood or protein in urine) in the first 3days after receiving the vaccination. What COVID vaccine side effects can and can't tell you about your body Findings include: Anaphylaxis after COVID-19 vaccination: 2-5 cases per million doses, or 1,655 reactions among the 331 million vaccines given as of July 10 (.0006%) Severe allergic reactions are not limited to COVID-19 vaccines; they can occur after any vaccine and are still exceedingly rare. The youngest child was 10months old. https://doi.org/10.4161/mabs.2.3.11782. 2005;385(Pt 3):8318. Non-IgE mediated responses to the lipid or PEG are also possible [93]. This annual initiative from UAB Employee Wellness that provides a free, 15-minute health screening to all benefit-eligible UAB, UAB Hospital, UAB LLC and UAB Health System/UA Health Services Foundation employees. A similar association has been reported for the smallpox and influenza vaccines [88, 89]. The side effects that we see occur early on, and thats it, Goepfert said. The greatest risk was found to be within three to seven days after the first dose of the vaccine. This is the body's natural response, as it's working hard to build immunity against the disease. The death rate due to TSS was 1.9 deaths per million vaccine doses in women ages 30 to 39 and 1.8 in women 40 to 49years of age. A comprehensive review of SARS-CoV-2 vaccines: Pfizer, Moderna & Johnson & Johnson. UAB also encourages applications from individuals with disabilities and veterans. Emotional intelligence is the top trait of effective leaders. Accessed 22 Mar 2020. One highlight is an interactive self-care plan that enables users to set goals and track their healthy habits, activities and mood each day. Seven patients who received sotrovimab (2%) reported serious adverse events as opposed to 27 patients (6%) in the placebo group. Ad26 vector-based COVID-19 vaccine encoding a prefusion-stabilized SARS-CoV-2 Spike immunogen induces potent humoral and cellular immune responses. https://doi.org/10.1002/hep.31487. Oral Side Effects of COVID-19 Vaccine - Full Text View - ClinicalTrials.gov Myocarditis cases reported after mRNA-based COVID-19 vaccination in the US from December 2020 to August 2021. B Well UAB helps students easily access resources on mobile devices and build a self-care plan that encourages healthy habits. The BLAZE-1 clinical trial also evaluated the combination of bamlanivimab and etesevimab, which did reduce viral load. They were initially identified from convalescent plasma obtained from COVID-19 survivors. Early indications are that Delta infections bring more severe side effects than other forms of COVID, but that vaccines are still protective against Delta. https://doi.org/10.1016/j.vaccine.2020.09.018. MAbs. Repeat dosing produced injection site reactions in 35% of the casirivimab and imdevimab group (252 people) compared to 16% in the placebo group (38 people). And in fact, this has never occurred with any vaccine.". We all have seen billboards and TV infomercials from law firms seeking people harmed by diet drugs or acid-reflux medicines for class-action lawsuits. Careers. UAB leadership expert Jean Ann Larson, Ed.D., explains how to take control, whether you are managing colleagues or your kids' fears. N Engl J Med. The Zoe app team from King's College London found: 37% experienced some local "after-effects", such as pain or swelling near the site of the injection, after their first dose, rising to about 45% . Mascellino MT, Di Timoteo F, De Angelis M, Oliva A. Overview of the main anti-SARS-CoV-2 vaccines: mechanism of action, efficacy and safety. PLoS One. 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