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PubMed1999

Salivary contribution to exhaled nitric oxide.

Dietary and metabolic nitrate is distributed from the blood to the saliva by active uptake in the salivary glands, and is reduced to nitrite in the oral cavity by the action of certain bacteria. Since it has been reported that nitric oxide may be formed nonenzymatically from nitrite this study aimed to determine whether salivary nitrite could influence measurements of exhaled NO. Ten healthy subjects fasted overnight and ingested 400 mg potassium nitrate, equivalent to approximately 200 g spinach. Exhaled NO and nasal NO were regularly measured with a chemiluminescence technique up to 3 h after the ingestion. Measurements of exhaled NO were performed with a single-breath procedure, standardized to a 20-s exhalation, at a flow of 0.15 L x s(-1), and oral pressure of 8-10 cmH2O. Values of NO were registered as NO release rate (pmol x s(-1)) during the plateau of exhalation. Exhaled NO increased steadily over time after nitrate load and a maximum was seen at 120 min (77.0+/-15.2 versus 31.2+/-3.0 pmol x s(-1), p<0.01), whereas no increase was detected in nasal NO levels. Salivary nitrite concentrations increased in parallel; at 120 min there was a four-fold increase compared with baseline (1.56+/-0.44 versus 0.37+/-0.09 mM, p<0.05). The nitrite-reducing conditions in the oral cavity were also manipulated by the use of different mouthwash procedures. The antibacterial agent chlorhexidine acetate (0.2%) decreased NO release by almost 50% (p<0.01) 90 min after nitrate loading and reduced the preload control levels by close to 30% (p<0.05). Sodium bicarbonate (10%) also reduced exhaled NO levels, but to a somewhat lesser extent than chlorhexidine acetate. In conclusion, salivary nitric oxide formation contributes to nitric oxide in exhaled air and a large intake of nitrate-rich foods before the investigation might be misinterpreted as an elevated inflammatory activity in the airways. This potential source of error and the means for avoiding it should be considered in the development of a future standardized method for measurements of exhaled nitric oxide.

Adult↗

PubMed2000

A study to assess the plaque inhibitory activity of a new triclosan mouthrinse formulation.

BACKGROUND/AIMS: Toothpastes and mouthrinses containing triclosan have been shown to be of some value at inhibiting both plaque and gingivitis. However much improved activity can be obtained by the addition of other chemicals which increase substantivity or antimicrobial activity. The present study was designed to determine whether a new mouthwash formulation containing a triglyceride oil was capable of reducing plaque reformation when compared to a control rinse containing neither triclosan or oil. METHODS: A total of 24 subjects took part in a double-blind, single-centre, cross-over study in which rinses were used as the only form of oral hygiene over a 4-day period. On the 1st day of each period, the subjects were given a prophylaxis to remove all plaque and calculus deposits. A single supervised rinse was taken and subsequent 2x daily rinses over the following 3 days. 24 and 96 h after the prophylaxis, the volunteers returned to the clinic, the plaque disclosed and assessed by plaque index and area. The test procedure and wash-out phase were repeated until all of the subjects had used both rinses. RESULTS: After 24 h, a 12% reduction in plaque score and a 25% reduction in plaque area was noted for the triclosan/oil rinse compared to the control rinse; however, these reductions were not significant (p>0.05). After 96 h, the triclosan/ oil rinse failed to produce a numerical or statistical reduction in plaque whether measured by plaque score or area. CONCLUSIONS: These findings would suggest that the triclosan/oil rinse would be of little value at inhibiting dental plaque whether used alone or as an adjunct to conventional oral hygiene measures.

Adult↗

PubMed2001

The effect of toothpaste on the propensity of chlorhexidine and cetyl pyridinium chloride to produce staining in vitro: a possible predictor of inactivation.

BACKGROUND/AIMS: Cationic antiseptics such as chlorhexidine (CHX) and cetyl pyridinium chloride (CPC) interact with dietary chromogens to produce extrinsic stain, and this can be used as a measure of activity of products. The aim of these studies in vitro was to determine if toothpaste influenced the tea staining effects of CHX and CPC as a predictor of action in vivo. METHOD: Clear acrylic specimens were soaked in pooled human saliva followed by sequential 2-min soaks in pairs of agents, namely 0.05% CHX, 0.05% CPC, 0.2% CHX, water (W) and toothpaste slurry (TP). The combinations were; TP/CHX, CHX/TP, TP/CPC, CPC/TP, W/CHX, CHX/W, W/CPC, CPC/W, TP/W, W/TP, W/W. These treatments were followed by a 60 min soak in tea. Optical density readings were taken at baseline and after each of 8 cycles. RESULTS: In the separate CHX and CPC studies by comparison with W/CHX, TP/0.05% CHX had little effect on staining, but TP/0.2% CHX showed a reduction in staining of 18%. 0.05% CHX/TP reduced staining by >40%, and 0.2% CHX by >78%. TP/CPC reduced staining by >26% and CPC/TP by 80%. Water after 0.2% CHX, 0.05% CHX and CPC reduced staining by 18%, 13% and 17% respectively. Little staining was seen with TP and W combinations. The data for CHX are in agreement with a study in vivo except TP followed by CHX reduced the activity of CHX. CONCLUSION: Toothpaste appears to adversely affect the activity of CHX and CPC particularly if used immediately after the antiseptics. The data further supports the concept of separating the use of antiseptics until sometime after the use of toothpaste, and the idea of developing mouthwash friendly toothpastes.

Acrylic Resins↗

PubMed2001

Effect of a polyhexamethylene biguanide mouthrinse on bacterial counts and plaque.

OBJECTIVES: For various clinical applications, polyhexamethylene biguanide (PHMB) has been used for many years as an antiseptic in medicine. Little is known, however, of its antibacterial activity in the oral cavity and its ability to inhibit plaque formation. In this study, a 0.04% PHMB mouthrinse (A) was compared with a negative control placebo rinse (10% ethanol, flavour) (B) and 2 positive control chlorhexidine rinses, one of which was a 0.12% aqueous solution (C) and the other a commercially available mouthrinse (Skinsept mucosa) diluted to a chlorhexidine concentration of 0.12% (D). MATERIAL AND METHODS: The study was a double-blind, randomised 4-replicate 4 x 4 Latin square cross-over design. Plaque regrowth was assessed with the Turesky et al. modification of the Quigley and Hein plaque index. The in vivo antibacterial effect was assessed by taking bacterial counts from the tooth surface (smears from the lingual surface of 16) and mucosa (smears from the buccal mucosa) 4 h after the 1st rinse with the preparations on day 1 and prior to the clinical examination on day 5. 16 volunteers participated, and on day 1 of each study period were rendered plaque-free, ceased toothcleaning, and rinsed 2x daily with the allocated mouthrinse. On day 5, plaque was scored and smears were collected according to the protocol. Washout periods were 9 days. Data were analysed using ANOVA with Tukey HSD adjustment for multiple comparisons (significance level alpha=0.05). RESULTS: Mouthrinses A, C, and D were significantly more effective in inhibiting plaque than the placebo (B). Mouthrinse C was significantly better than mouthrinses A and D, while mouthrinses D and A were equally effective in inhibiting plaque. Bacterial count reductions on the tooth surface with mouthrinse C were significantly greater compared to mouthrinse A and the placebo (B). The reduction of bacterial counts on the mucosa with C was significantly greater than with A and B after 4 h and significantly greater than with A, B and D after 5 days. Mouthrinse A reduced bacteria on the mucosa significantly more effectively than the placebo (B) after 4 h and 5 days, while mouthrinse D was more effective than the placebo (B) after 4 h. CONCLUSION: The results indicate that a 0.04% PHMB mouthwash inhibits plaque regrowth and reduces oral bacterial counts, and may be used in preventive applications in the oral cavity.

Adult↗

PubMed2002

The effect of a polyhexamethylene biguanide mouthrinse compared to an essential oil rinse and a chlorhexidine rinse on bacterial counts and 4-day plaque regrowth.

OBJECTIVES: For various clinical applications, polyhexamethylene biguanide hydrochloride (PHMB) has been used for many years as an antiseptic in medicine. Recently, a 0.04% PHMB mouthwash was shown to inhibit plaque regrowth and to reduce oral bacterial counts. In this study, a 0.12% PHMB mouthrinse (A) was compared with a negative control placebo rinse (10% ethanol, flavour) (B), a positive control 0.12% chlorhexidine rinse (C), and a commercially available mouthrinse containing essential oils (Listerine) (D). MATERIALS AND METHODS: The study was a double-blind, randomised 4-replicate 4 x 4 Latin square cross-over design in which plaque regrowth was measured. The in vivo antibacterial effect was assessed by taking bacterial counts from the tooth surface and mucosa 4 h after the first rinse with the preparations on day 1 and prior to the clinical examination on day 5. 16 volunteers participated and, on day 1 of each study period, were rendered plaque-free, ceased toothcleaning, and rinsed 2x daily with the allocated mouthrinse. On day 5, plaque was scored and smears were collected according to the protocol. Washout periods were 9 days. Data were analysed using ANOVA with Bonferroni HSD adjustment for multiple comparisons (significance level alpha=0.05). RESULTS: The 0.12% PHMB mouthrinse (A) was significantly more effective in inhibiting plaque than the placebo (B) but no significant differences could be observed between A and 0.12% chlorhexidine (C), or between A and Listerine (D). Bacterial count reductions on the tooth surface with PHMB (A) were significantly greater compared to the placebo (B) after 4 h and significantly greater compared to B and D after 5 days. Chlorhexidine (C) was more effective than A after 5 days. On the mucosa, chlorhexidine (C) was significantly more effective in reducing bacterial counts than the other 3 treatments at both time points investigated. PHMB (A) was significantly more effective in reducing bacterial counts than the placebo (B) after 4 h and after 5 days, and than D after 4 h. CONCLUSION: Consistent with a previous study, a PHMB mouthrinse was shown to inhibit plaque recolonisation and to reduce oral bacterial counts, indicating that PHMB may find applications in the prevention of plaque-associated diseases.

Adult↗

PubMed2003

Improving oral health: current considerations.

The high incidence of periodontal disease among adults in the Western world indicates that in most cases, routine dental care could be considerably improved. The progressive effect of the disease suggests that improvements in oral cleanliness are mandatory if large numbers of adults are to retain their teeth into old age. Data show that periodontal disease can be minimized through effective plaque control, and that a combination of brushing, interdental cleaning, and chemotherapeutic agents (e.g. mouthwash) is beneficial to patients with plaque control problems. The vast majority of adults do not follow an adequate home-care routine. Average brushing times are low, and only a minority of patients regularly floss. In addition, in those patients who do regularly brush and floss, a deterioration of plaque control occurs over time, suggesting that compliance is a major issue. The principal challenge for dental professionals is to identify how best to elicit an improvement.

Adult↗

PubMed2003

Recent concepts in plaque formation.

Dental plaque is an adherent, bacterial film, and is the main pathological agent for periodontal diseases. The formation of dental plaque can occur both supragingivally and subgingivally. The development of plaque is a three-step process. Following the formation of a pellicle, pioneer micro-organisms will adhere to it, proliferate and form colonies. The final stage involves the aggregation of filamentous organisms and spirochetes into a cohesive biofilm. Many products of the plaque bacteria reach the subepithelial tissue, causing inflammatory responses such as increased vascularity and leukocyte diapedesis. Both supragingival and subgingival plaque may form a hard, mineralized mass called calculus. The surface of calculus harbours bacteria, which may exacerbate the inflammatory responses. An effective oral antiseptic must be active against a wide range of Gram-positive and Gram-negative bacterial species, including streptococci and fusobacteria. Ideally, an effective agent would also penetrate the plaque biofilm. Data show that essential oil and chlorhexidine mouthwashes have the broadest antimicrobial effects.

Anti-Infective Agents, Local↗

PubMed2002

The effect of commercially available saliva substitutes on predemineralized bovine dentin in vitro.

OBJECTIVE: The objective of this study was to evaluate the effects of various saliva substitutes (Artisial; Glandosane; Oralube; Saliva medac; Oralbalance) on the lesion depth and the mineral content of predemineralized bovine dentin in vitro. MATERIALS AND METHODS: Ninety-six dentin samples were prepared from 24 freshly extracted bovine incisors. The samples were predemineralized (pH 5.5; 10 days), and subsequently exposed to the various artificial salivas. A carbonate-reduced mineral water (Hirschquelle) as well as the mouthwash solutions Meridol and biotène served as controls. Lesion depth and mineral loss were evaluated from microradiographs of thin sections (110 microm) by a dedicated software package (TMR 1.24). RESULTS: After storage in Glandosane and biotène, the results indicated a significant mineral loss and an increase in lesion depth (P < 0.01; Wilcoxon). In contrast, specimens stored in Oralube showed a decrease in lesion depth and an increase in mineral content (P < 0.05; Wilcoxon). CONCLUSIONS: Thus, the use of neither Glandosane nor biotène can be recommended in dentate patients with severe xerostomia.

Amines↗

PubMed2002

Dental erosion in a group of British 14-year-old, school children. Part III: Influence of oral hygiene practises.

OBJECTIVES: The aims of this study were firstly to describe the dental history and oral hygiene practises in a cluster random sample of 14-year-old children in Birmingham, UK. The second aim was to determine whether the oral hygiene practises are associated with dental erosion. METHOD: A total of 418, 14-year-old schoolchildren from a cluster random sample in Birmingham, UK were assessed for dental erosion (209 males and 209 females). Data on the dental history and oral hygiene practises were obtained from a self-reported questionnaire supplemented by a structured interview. The data were analysed using SPSS with Mann-Whitney U analyses and odds ratios. RESULTS: 74% of the teenagers claimed to attend the dentist on a six-monthly basis; 60% brushed their teeth twice a day ie before breakfast and last thing at night, 25% once a day, 12% three times or more a day and 3% less than once a day. It was a so found that 28% of the children brushed their teeth after meals; 92% of the children used a manual toothbrush and 56% of them replaced their toothbrush every three-months. The most common technique used by the children was a circular brushing movement; 44% of them used a mouthwash and 40% used other interdental cleaning. Girls brushed their teeth more frequently than boys. Associations were found between dental erosion and brushing teeth last thing at night, after meals, techniques of brushing teeth, and type of toothbrush and frequency of brushing. It was concluded that reported oral hygiene practises in teenage schoolchildren in Birmingham, UK complied with generally recommended guidelines. However, there was an association between dental erosion and some of these oral hygiene practises. Advice concerning the impact of some oral hygiene procedures needs to be given to those who are susceptible to dental erosion.

Adolescent↗

PubMed1997

A rapid non-invasive method for the detection of the haemochromatosis C282Y mutation.

We describe the rapid single-step detection, by mutagenically separated polymerase chain reaction (MS-PCR), of the HLE C282Y mutation, for which > 90% of haemochromatosis patients in the U.K. are homozygous. In addition to using purified DNA as a template, whole blood and lysed buccal cell extracts from mouthwash samples can be used. Therefore sample collection may be non-invasive and purification steps kept to a minimum.

Genetic Techniques↗

PubMed2000

Management of anticoagulation in patients with prosthetic heart valves undergoing oral and maxillofacial operations.

There is wide variation in the management of patients with mechanical prosthetic valves who are taking anticoagulants and who require non-cardiac surgery. In this paper, we outline a pragmatic, practical approach to the adjustment of anticoagulation in relation to both the degrees of surgical trauma during oral and maxillofacial surgery and the risk of thromboembolism associated with the prosthetic valve. For minor surgery, no adjustment of anticoagulation is undertaken if the International Normalized Ratio is less than 4.0, if local haemostatic methods and tranexamic acid mouthwashes are used. For major surgery, warfarin is stopped preoperatively and low-molecular-weight heparin is used. For emergency surgery, partial reversal of anticoagulation with low-dose parenteral vitamin K is obtained.

Administration, Oral↗

PubMed2002

Fluticasone propionate spray and betamethasone sodium phosphate mouthrinse: a randomized crossover study for the treatment of symptomatic oral lichen planus.

BACKGROUND: Symptomatic oral lichen planus (OLP) has been palliated with a wide spectrum of topical and systemic therapies. Although the majority of management strategies include corticosteroids, few have been evaluated in randomized controlled trials. OBJECTIVE: We investigated the acceptability and efficacy of topical fluticasone propionate spray (FP) and betamethasone sodium phosphate mouthrinse (BSP) upon the signs and symptoms of OLP, assessing patient quality of life changes as a consequence of these therapies. METHODS: We implemented a randomized, crossover study in which each drug was administered for a period of 6 weeks with an intervening washout period of 2 weeks at an outpatient oral medicine unit in London, United Kingdom. We treated 48 patients with biopsy-proven symptomatic OLP, and 44 patients (92%) completed the study. The dosage was 50 microg two dose unit sprays and BSP 500 microg, each 4 times daily. Symptomatic improvement was evaluated by means of a visual analogue scale (VAS), the McGill pain score, the Oral Health Impact Profile (OHIP), and Oral Health Quality of Life (OHQoL) questionnaires. The total surface area of the lesions, including all white, erythematous, and ulcerative lesions was measured at each visit. The efficacy, ease of application, and adverse effects associated with each medication were recorded. RESULTS: Both FP and BSP mouthwash caused both a statistically significant reduction in painful symptoms as measured by the VAS and improvement in quality of life as measured by the OHIP and OHoQL indices. There was no significant difference between the two corticosteroids in their efficacy in reducing painful symptoms (measured by the VAS) or in their effect on patient quality of life. Both FP and BSP significantly reduced the surface area of oral lesions. However, FP was statistically significantly better than BSP in reducing lesion surface area. There was no statistically significant difference between the patient-assessed effects of the 2 therapies. CONCLUSIONS: FP and BSP are both effective in the short-term clinical management of symptomatic OLP. FP is more acceptable to patients than BSP because of the convenience of the spray form.

Administration, Topical↗

PubMed2003

Budesonide: a novel treatment for oral chronic graft versus host disease.

OBJECTIVE: This clinical trial aims to evaluate the efficacy of budesonide, a newly registered steroid with high potency and low bioavailability, for the treatment of chronic oral graft versus host disease (GVHD). STUDY DESIGN: Twelve patients with chronic resistant oral GVHD were treated with 3 mg budesonide/5 ml saline 2 to 3 times a day for up to 3 months. Oral manifestations were monitored, and mucosal response scored. RESULTS: All patients responded positively to the mouthwash, and 7 of the 12 patients were scored as having "good" or "complete" recovery by both examiner and subject. An early response noted within the first 2 to 3 weeks of treatment was complemented by a probable cumulative effect seen during the first months of treatment. CONCLUSION: Budesonide is suggested as an alternative treatment for chronic oral GVHD.

Adult↗

PubMed2005

Generation of volatile compounds on mouth exposure to urea and sucrose: implications for exhaled breath analysis.

The increase in ammonia and ethanol in the exhaled breath stream following mouthwashes by aqueous solutions of urea and sugar (sucrose), respectively, has been investigated by analysing exhaled breath in real time using selected ion flow tube mass spectrometry, SIFT-MS. It is shown that the measured levels of these compounds in the stream of exhaled breath can be much greater than the endogenous levels originating at the alveolar boundary. Thus, it is concluded that without careful preparation, mouth production of these compounds, and other compounds as yet unidentified, can seriously compromise the quantification of truly endogenous trace compounds present in blood and in the alveolar breath, as required for clinical diagnosis, and can probably introduce additional compounds into the breath stream that could seriously mislead breath analysis. The concentrations of both the urea and sucrose solutions used to enhance the ammonia and ethanol levels were larger than normally present in food and drinks and so in most situations such severe enhancements will not occur.

Ammonia↗

PubMed1991

Decreased oral toxicity with the local use of allopurinol in patients who received high dose 5-fluorouracil.

5-Fluorouracil (5FU) is the most effective drug in gastrointestinal cancer. Mucositis and bone marrow toxicity are the two major limiting side effects. In our effort to reduce mucositis we administered Allopurinol mouthwash in 42 patients who had experienced oral mucositis during prior treatment with 5FU. In all patients significant reduction of oral toxicity was noticed as well as prolonged pain relief.

Allopurinol↗

PubMed1994

Efficacy of topical amoxicillin plus clavulanate/ticarcillin plus clavulanate and clindamycin in contaminated head and neck surgery: effect of antibiotic spectra and duration of therapy.

This prospective, randomized trial was designed to determine the efficacy and mechanism of action of topical mouthwash versus parenterally administered perioperative prophylactic antibiotics in contaminated head and neck surgery. Patients were randomly assigned to 1 of 4 treatment groups: 1 day of parenteral clindamycin (standard prophylaxis), 1 day of topical clindamycin, 5 days of topical clindamycin, or 1 day of topical amoxicillin plus clavulanate/ticarcillin plus clavulanate. Patients who received the latter regimen had fewer bacteria postoperatively compared with the other 3 treatment groups. The number of gram-negative aerobic bacilli on postoperative oral cavity cultures was increased in all 3 clindamycin groups but not in the amoxicillin plus clavulanate/ticarcillin plus clavulanate group. Parenteral clindamycin appears to exert its effect by being in the neck tissues at the time of surgery; however, all 3 topical regimens were more effective at reducing the number of bacteria in the neck viscera. Topical antibiotic prophylaxis was simple, safe, effective, and well tolerated.

Amoxicillin↗

PubMed1998

Response of single species biofilms and microcosm dental plaques to pulsing with chlorhexidine.

The aim of this study was to determine the effect of pulsing chlorhexidine gluconate, at concentrations commonly used in mouthwashes, on Streptococcus sanguis biofilms and microcosm dental plaques in vitro. Biofilms were grown on bovine enamel and nutrients were supplied in the form of artificial saliva. Pulsing experiments were carried out on steady-state biofilms using 0.05 or 0.2% chlorhexidine solutions delivered twice daily for 1 min. In a separate study, the enamel discs on which the biofilms were formed were pre-treated with chlorhexidine and pulsed directly after inoculation and then at regular intervals. With both concentrations of chlorhexidine used, a c.2 log10 reduction in the viable counts of S. sanguis was achieved with the initial pulse, but as pulsing continued, the bacterial population recovered, albeit not to the previous level. A c.1 log10 reduction in the total viable counts of the microcosm plaques was seen after the first pulse with 0.2% chlorhexidine. The total count then recovered rapidly and, after the fifth pulse, the total viable counts were not significantly different from those before pulsing. The total counts then remained at a similar level throughout the course of the experimental runs. Pre-treatment of the enamel discs with 0.2% chlorhexidine before inoculation produced viable counts of c.10(5) cfu/mm2, a 1 log10 reduction compared with untreated discs. After pulsing with 0.2% chlorhexidine at 8 h, a 3 log10 reduction was seen in the total aerobic and anaerobic counts, but again the viable counts subsequently increased despite twice-daily chlorhexidine pulsing. Regardless of the nature of the biofilm, pulsing initially achieved substantial kills, but the viability of the biofilms subsequently increased despite continued pulsing. Chlorhexidine was effective at reducing the viability of microcosm plaques when it was applied to the substratum before exposure to bacteria and subsequently pulsed on to the biofilms.

Animals↗

PubMedDate not supplied

Topical transforming growth factor-beta3 in the prevention or alleviation of chemotherapy-induced oral mucositis in patients with lymphomas or solid tumors.

Transforming growth factor (TGF)-beta3 has been hypothesized to prevent or alleviate oral mucositis (OM) in cancer patients receiving high-dose chemotherapy (CT). Two double-blind, placebo-controlled, multicenter, phase II studies of TGF-beta3 were initiated in the United States, Europe, and Argentina in patients with lymphomas or solid tumors who were receiving highly stomatotoxic CT regimens. Patients were to apply 10-mL mouthwash applications of TGF-beta3 (25 microg/mL) or placebo four times daily (or twice daily) 1 day before and all days during CT. The patients were subsequently evaluated for OM incidence, severity, and duration using National Institute of Cancer Common Toxicity Criteria (NCI-CTC) criteria and an objective scoring system (1). After the start of the trials, negative results from new preclinical studies suggesting suboptimal formulation and/or dosing led to an interim analysis of the ongoing clinical trials. One hundred fifty-two patients from the combined studies were included in the interim analysis, with 116 patients on the TGF-beta3 four times daily and placebo arms. Most (72%) patients had breast cancer, 22% had lymphomas, and 6% had other solid tumors. Although 98% (149 of 152) of patients experienced adverse events, only 14% (22 of 152) experienced events that were judged as possibly or probably related to the study drug (primarily gastrointestinal symptoms). No clinically relevant differences were seen between the treatment and placebo arms regarding safety, nor was there evidence for systemic absorption of TGF-beta3. Finally, there was no advantage of TGF-beta3 treatment regarding the incidence (TGF-beta3 four times daily versus placebo [46% versus 47%]), onset, or duration of NCI-CTC grade 3 or 4 OM. For this dose, formulation, regimen. and patient population, TGF-beta3 was not effective in the prevention or alleviation of CT-induced OM.

Adult↗