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Young Ho Lee

Publications and source records attributed to Young Ho Lee.

At least 19 recordsLinked to original sources

The association between hyperuricemia and the Trp64Arg polymorphism of the beta-3 adrenergic receptor.

The object of this study was to determine the association of Trp64Arg polymorphism with hyperuricemia. This study is an age-matched, case-controlled study of 203 hyperuricemic and 203 normouricemic men. The frequency of genotypes was compared between the two groups. Possible confounding metabolic variables were included in a multiple logistic regression model for multivariate adjustment. The genotype frequencies of Trp64Trp, Trp64Arg, and Arg64Arg in hyperuricemic and normouricemic groups are respectively 130, 69, and 4 (64.0%, 34.0%, 2.0%) and 154, 45, and 4 (75.9%, 22.2%, 2.0%) (P = 0.029, Chi-square test). Simple logistic regression analysis indicated that the Trp64Arg genotype is significantly associated with hyperuricemia (OR = 1.816, 95% CI (1.167-2.827), P = 0.008). Multivariate analysis for controlling metabolic effects also showed a significant association with the occurrence of hyperuricemia (OR = 1.937, 95% CI (1.149-3.266), P = 0.013). Trp64Arg polymorphism of the beta-3 adrenergic receptor may be independently associated with hyperuricemia in males.

Adult↗

Adjusted indirect comparison of celecoxib versus rofecoxib on cardiovascular risk.

To compare the magnitude of celecoxib versus rofecoxib on the cardiovascular risk. We performed adjusted indirect comparison of celecoxib versus rofecoxib for cardiovascular events using two data on The Adenomatous Polyp Prevention on Vioxx (APPROVe) trial and Adenoma Prevention with Celecoxib (APC) trial. Baseline characteristics of the patients and placebos were comparable in both trials, in terms of age, sex, hypertension, diabetes mellitus, smoking, and hypercholesterolemia. The overall incidence of cardiovascular events was similar in both groups (rofecoxib 48/1,287 versus celecoxib 48/1,356, p = 0.79). The relative risks (RRs) of all myocardial infarction or sudden death from cardiac causes were increased in both rofecoxib and celecoxib groups [rofecoxib versus placebo; RR 1.35, 95% confidence interval (CI) 1.07-1.69, p = 0.03, celecoxib versus placebo; RR 1.35, 95% CI 1.14-1.51, p = 0.01]. The RRs for cardiovascular events derived from the adjusted indirect comparisons of the two coxibs did not significantly differ from unity (celecoxib versus rofecoxib; RR 0.95, 95% CI 0.76-1.19, p = 0.67). The adjusted indirect comparison analysis shows that celecoxib and rofecoxib may have similarly effect of cardiovascular events when used for 3 years.

Adenoma↗

Tumor necrosis factor-alpha promoter -308 A/G polymorphism and rheumatoid arthritis susceptibility: a metaanalysis.

OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) promoter -308 A/G polymorphism has been reported to be associated with rheumatoid arthritis (RA) with inconsistent results. We investigated whether TNF-alpha -308 A/G polymorphism confers susceptibility to RA. METHODS: We conducted a random effect metaanalysis on the association of genotypes A/A (recessive effect), A/A + A/G (dominant effect), A allele, and A/A vs G/G genotypes of the TNF-alpha -308 polymorphisms with RA overall and within different ethnic populations. RESULTS: Fourteen studies, 10 of Europeans, 3 of Latin Americans, and one Asian, were included in this metaanalysis. An association between RA and the TNF-alpha -308 A allele was not found in the overall population (OR 1.005, 95% CI 0.715-1.412, p = 0.976). However, stratification by ethnicity indicated that the TNF-alpha A allele was significantly associated with RA in Latin Americans (OR 2.004, 95% CI 1.158-3.467, p = 0.013). Conversely, there was no association detected for the TNF-alpha A allele with RA patients from the European samples (OR 0.911, 95% CI 0.684-1.212, p = 0.520). The OR for the A/A + A/G genotype, the A/A genotypes, and the A/A vs G/G genotypes in samples overall and in each ethnic group showed a similar trend to those for the TNF-alpha A allele. CONCLUSION: This metaanalysis demonstrates that the TNF-alpha -308 A/G polymorphism may represent a significant risk factor for RA in Latin Americans, but not in Europeans.

Alleles↗

Epigenetic changes in estrogen receptor beta gene in atherosclerotic cardiovascular tissues and in-vitro vascular senescence.

Epigenetic changes marked by DNA methylation have been proposed to play a role in age-related disease. We investigated DNA methylation changes in cardiovascular atherosclerotic tissues and in-vitro vascular senescence in the promoter of estrogen receptor beta gene, which has essential roles in vascular function. Coronary atherosclerotic tissues showed higher methylation levels (28.7%) than normal appearing arterial (6.7%-10.1%) and venous tissues (18.2%). In comparing estrogen receptor beta methylation between plaque and non-plaque regions in ascending aorta, common carotid artery, and femoral artery of two patients, the plaque lesions showed consistently higher methylation levels than non-plaque regions. Passage-dependent increased estrogen receptor beta methylation was observed in three of six human aortic endothelial or smooth muscle cell lines cultured in-vitro to vascular senescence. Estrogen receptor beta expression in these vascular cell lines was significantly activated by DNA-methyltransferase inhibition. This activity was augmented by histone deacetylase inhibition. These findings provide evidence of epigenetic dysregulation of estrogen receptor beta in atherosclerosis and vascular aging. We suggest that focal epigenetic changes in estrogen receptor beta contribute to the development of atherosclerosis and vascular aging.

Arteries↗

Osteoarthritis susceptibility loci defined by genome scan meta-analysis.

Genome scans for osteoarthritis (OA) have yielded inconsistent results. The absence of replication of linkage might be due to lack of power of individual studies. A meta-analysis of the published data was performed to assess evidence for linkage of OA across genome scan studies. Three OA whole-genome scans including 893 families with 3,000 affected individuals were used for genome scan meta-analysis (GSMA). A total of 5 bins lie above 95% confidence level (P = 0.05) and 1 bin is above 99% confidence level (P = 0.01) in OA GSMA; bins 7.6 (7q34-7q36.3, Psumrnk = 0.0035), 11.3 (11p12-11q13.4), 6.3 (6p21.1-6q15), 2.8 (2q31.1-2q34) and 15.3 (15q21.3-15q26.1). The highest summed rank was observed at bin 7.6. In conclusion, the OA GSMA has shown chromosome 7q34-7q36.3 with the highest summed rank and four additional loci with significant summed ranks across studies.

Chromosomes, Human, Pair 7↗

Association of TNF-alpha -308 G/A polymorphism with responsiveness to TNF-alpha-blockers in rheumatoid arthritis: a meta-analysis.

Tumor necrosis factor (TNF) antagonists are among the most effective therapies for rheumatoid arthritis (RA), yet not all patients show a response. Using meta-analysis, this present study was designed to investigate whether or not the TNF-alpha promoter -308 A/G polymorphism is associated with responsiveness to anti-TNF therapy in RA patients. We performed an exhaustive search for studies that examined the association of the TNF-alpha promoter -308 A/G polymorphism and responsiveness of anti-TNF therapy in RA using MEDLINE citations and manual review. Meta-analysis was performed for A allele carrier (genotypes A/A + A/G) between responders to anti-TNF therapy and a non-responder group in a random effects model. A total of 6 studies met the inclusion criteria. The number of patients in individual studies ranged from 33 to 123. There were 311 RA patients who were included in this meta-analysis. There was no heterogeneity between studies (I (2) = 0%, P = 0.42). The overall OR for the A allele carrier status was significantly decreased in the responder group (OR = 0.33, 95% confidence interval = 0.17-0.63, P = 0.0008). The frequency of the A allele carrier was 53/240 (22.1%) in responders and 32/71 (45.1%) in non-responders. Patients not responding to anti-TNF therapy showed an increased frequency of the A allele. The meta-analysis of the available data shows a significant association between the TNF-alpha promoter -308 A/G polymorphism and responsiveness to anti-TNF therapy, suggesting that the individuals with RA who carry the A allele have a poorer response to anti-TNF therapy than those with the G allele.

Antirheumatic Agents↗

Prostaglandin E2 augments IL-10 signaling and function.

In inflamed joints of rheumatoid arthritis, PGE(2) is highly expressed, and IL-10 and IL-6 are also abundant. PGE(2) is a well-known activator of the cAMP signaling pathway, and there is functional cross-talk between cAMP signaling and the Jak-STAT signaling pathway. In this study, we evaluated the modulating effect of PGE(2) on STAT signaling and its biological function induced by IL-10 and IL-6, and elucidated its mechanism in THP-1 cells. STAT phosphorylation was determined by Western blot, and gene expression was analyzed using real-time PCR. Pretreatment with PGE(2) significantly augmented IL-10-induced STAT3 and STAT1 phosphorylation, as well as suppressors of cytokine signaling 3 (SOCS3) and IL-1R antagonist gene expression. In contrast, PGE(2) suppressed IL-6-induced phosphorylation of STAT3 and STAT1. These PGE(2)-induced modulating effects were largely reversed by actinomycin D. Pretreatment with dibutyryl cAMP augmented IL-10-induced, but did not change IL-6-induced STAT3 phosphorylation. Misoprostol, an EP2/3/4 agonist, and butaprost, an EP2 agonist, augmented IL-10-induced STAT3 phosphorylation and SOCS3 gene expression, but sulprostone, an EP1/3 agonist, had no effect. H89, a protein kinase A inhibitor, and LY294002, a PI3K inhibitor, diminished PGE(2)-mediated augmentation of IL-10-induced STAT3 phosphorylation. In this study, we found that PGE(2) selectively regulates cytokine signaling via increased intracellular cAMP levels and de novo gene expression, and these modulating effects may be mediated through EP2 or EP4 receptors. PGE(2) may modulate immune responses by alteration of cytokine signaling in THP-1 cells.

Adjuvants, Immunologic↗

Tumor necrosis factor-alpha and interleukin-1beta increases CTRP1 expression in adipose tissue.

CTRP1, a member of the CTRP superfamily, consists of an N-terminal signal peptide sequence followed by a variable region, a collagen repeat domain, and a C-terminal globular domain. CTRP1 is expressed at high levels in adipose tissues of LPS-stimulated Sprague-Dawley rats. The LPS-induced increase in CTRP1 gene expression was found to be mediated by TNF-alpha and IL-1beta. Also, a high level of expression of CTRP1 mRNA was observed in adipose tissues of Zucker diabetic fatty (fa/fa) rats, compared to Sprague-Dawley rats in the absence of LPS stimulation. These findings indicate that CTRP1 expression may be associated with a low-grade chronic inflammation status in adipose tissues.

Adipokines↗

Osteoarthritis susceptibility loci defined by genome scan meta-analysis.

Genome scans for osteoarthritis (OA) have yielded inconsistent results. The absence of replication of linkage might be due to the lack of power of individual studies. A meta-analysis of published data was performed to assess evidence for linkage of OA across genome scan studies. Three OA whole-genome scans including 893 families with 3,000 affected individuals were used for genome scan meta-analysis (GSMA). A total of five bins lie above 95% confidence level (P=0.05) and one bin is above 99% confidence level (P=0.01) in OA GSMA; bins 7.6 (7q34-7q36.3, P (sumrnk) =0.0035), 11.3 (11p12-11q13.4), 6.3 (6p21.1-6q15), 2.8 (2q31.1-2q34) and 15.3 (15q21.3-15q26.1). The highest summed bin was bins 7.6. In conclusion, the OA GSMA has shown that chromosome 7q34-7q36.3 have the highest summed rank and four additional loci with significant summed ranks across studies.

Chromosomes, Human, Pair 7↗

Meta-analysis of genome-wide linkage studies for bone mineral density.

Genome-wide linkage studies have shown several chromosome loci that may harbor genes that regulate bone mineral density (BMD), but results have been inconsistent. A meta-analysis was performed to assess evidence for linkage of BMD across whole genome scan studies. Eleven whole-genome scans of BMD or osteoporosis containing 3,097 families with 12,685 individuals were included in this genome scan meta-analysis (GSMA). For each study, 120 genomic bins of approximately 30 cM were defined and ranked according to maximum evidence for linkage within each bin. Bin ranks were weighted and summed across all studies. The summed rank for each bin was assessed empirically for significance using permutation methods. A total of seven bins lie above the 95% confidence level (P=0.05) and one bin was above the 99% confidence level (P=0.01) in the GSMA of eleven linkage studies: bins 16.1 (16pter-16p12.3, Psumrnk <0.01), 3.3 (3p22.2-3p14.1), 1.1 (1pter-1p36.22), 18.2 (18p11.23-18q12.2), 6.3 (6p21.1-6q15), 20.1 (20pter-20p12.3), and 18.1 (18pter-18p11.23). GSMA was performed with seven studies with linkage scores of LOD >1-1.85 for sensitivity test, confirming the linkage on chromosome 16p and 3p and revealing evidence of new linkage in bins 10.2 (10p14-10q11.21) and 22.2 (22q12.3-22pter). In conclusion, the meta-analysis of whole-genome linkage studies of BMD has shown chromosome 16pter-16p12.3 to have the greatest evidence of linkage as well as revealing evidence of linkage in chromosomes 1p, 3p, 6, 10, 18, 20p, and 22q across studies. This data may provide a basis with which to carry out targeted linkage and candidate gene studies particularly in these regions.

Bone Density↗

Trans-cultural comparison of disordered eating in Korean women.

OBJECTIVE: The presence of eating disorders in non-Western cultures is often attributed to the export of Western ideals. This study examines this hypothesis by comparing disordered eating attitudes and behaviors in Korean women with differing levels of exposure to Western culture. METHOD: Second-generation Korean-Americans (n=167) and Korean immigrants (n=37) completed the Eating Attitudes Test (EAT-26), and data from native Koreans (n=937) were obtained from a previous epidemiological study, using a Korean-translated version of the EAT-26 (K-EAT-26). Korean-American and immigrant women completed the Suinn-Lew Asian Self-Identity Acculturation Scale (SL-ASIA). RESULTS: Korean-American women scored significantly lower on the EAT-26 than Korean immigrants and native Koreans, who did not differ from each other. Korean-Americans were more Western-oriented than Korean immigrants, and acculturation levels were not correlated with EAT-26 scores in either group. CONCLUSION: This study supports the importance of native cultural factors in the development of eating disorders in non-Western contexts.

Acculturation↗

Nasal bone length at 11-14 weeks of pregnancy in the Korean population.

OBJECTIVES: The aim of this study was to provide reference values for nasal bone length (NBL) scanned at 11-14 weeks' gestation in the Korean population and compare these values with those of the Caucasian and African-American populations. METHODS: From April 2004 to July 2004, fetal NBLs were measured in well-dated, non-anomalous fetuses at 11-14 weeks' gestation in the Korean population. Regression analysis was used to assess the relationship between NBL and crown-rump length (CRL), and reference values including the 5th, 50th, and 95th percentile were calculated for each gestational age. The reference values in our study were compared with those of the Caucasian and African-American populations. RESULTS: A total of 982 cases were prospectively included in the study. NBL increased linearly with advance in CRL and was described by the equation; NBL (mm) = 0.433 + 0.022 x CRL (mm), R(2) = 0.37. The median values (5%, 95%) were 1.5 mm (1.2 mm, 1.9 mm), 1.7 mm (1.4 mm, 2.1 mm), 1.9 mm (1.6 mm, 2.3 mm), and 2.1 mm (1.7 mm, 2.6 mm) for 11, 12, 13, and 14 weeks' gestation, respectively. The median values for each gestational age in the Korean population were significantly lower than those in the Caucasian and African-American populations (P < 0.0001). CONCLUSION: There is a difference in NBL scanned at 11-14 weeks' gestation between the Korean and the Caucasian/African-American populations, and so racial adjustment is needed in the evaluation of the fetal nasal bone for current first-trimester screening.

Black or African American↗

Abnormal triangular epiphysis causing angular deformity of the thumb.

PURPOSE: To present a triangular-shaped abnormal secondary ossification center of the distal phalanx causing angular deformity of the thumb and the surgical outcome of corrective closing-wedge osteotomy for this deformity. METHODS: We treated 6 patients with abnormal triangular epiphysis in the distal phalanx of the thumb, including 3 bilateral cases. The average age was 43 months and there were 2 boys and 4 girls. Of the 9 thumbs intraepiphyseal closing-wedge osteotomy was performed in 5 and proximal phalangeal closing-wedge osteotomy was performed in 4. We measured the deformities in degrees of angulation and the range of motion of the interphalangeal (IP) joint. The average duration of the follow-up period was 27 months after the surgery. RESULTS: Preoperative angular deformity of ulnar deviation averaged 30 degrees , which was reduced to an average of 12 degrees after osteotomy at the last follow-up assessment. All osteotomies healed and there was no evidence of physeal or articular damage. Interphalangeal joint range of motion did not decrease after surgery in all cases. Patients and parents were satisfied with the results of the surgery, although mild deformity persisted in the interphalangeal joint when in the flexed position after proximal phalangeal osteotomy. CONCLUSIONS: Abnormal triangular epiphysis causing angled thumb is different from delta bone and can be treated with either intraepiphyseal or proximal phalangeal closing-wedge osteotomy. The intraepiphyseal procedure, however, could achieve better deformity correction regardless of the interphalangeal joint position. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic, Level IV.

Child, Preschool↗

Meta-analysis of TNF-alpha promoter -308 A/G polymorphism and SLE susceptibility.

Alleles of tumor necrosis factor-alpha (TNF-alpha) gene have been inconsistently associated with systemic lupus erythematosus (SLE), particularly the 308-A/G functional promoter polymorphism. To generate large-scale evidence on whether 308-A/G promoter polymorphism is associated with SLE susceptibility we have conducted a meta-analysis. We have identified 21 studies of this polymorphism and SLE using MEDLINE search. Meta-analysis was performed for genotypes A/A (recessive effect), A/A+A/G (dominant effect), and A allele in fixed or random effects models. All control samples were in Hardy-Weinberg proportion. The overall odds ratio (OR) of the A/A genotype was 3.2 (95% CI=2.0-5.3, P<0.001). Stratification by ethnicity indicated that the A/A genotype was associated with SLE in European-derived population (OR=4.0, CI=2.5-6.4, P<0.001). No association was detected in Asian-derived population (OR, 1.3, CI=0.3-6.3, P=0.76). The overall OR for the risk genotypes (A/A and A/G) was 2.0 (CI=1.3-3.1, P<0.001). Similar results were found between the risk allele A and SLE where a significant association was found in European population (OR=2.1, CI=1.6-2.7, P<0.001), but not in Asian (OR=1.4, CI=0.8-2.3, P=0.2) or African (OR=1.2, CI=0.6-2.5, P=0.59) populations. In summary, this meta-analysis demonstrates that the TNF-alpha promoter -308 A/G polymorphism may confer susceptibility to SLE, especially in European-derived population.

Alleles↗

Innervated lateral middle phalangeal finger flap for a large pulp defect by bilateral neurorrhaphy.

BACKGROUND: The dorsal middle phalangeal finger flap is a reliable flap. However, it requires skin grafting on the whole surface of the dorsum of the middle phalanx of the donor finger for an exposed extensor tendon and leaves a conspicuous contour deformity at the donor site. In an effort to overcome this problem, the authors have been using a heterodigital innervated lateral middle phalangeal finger flap for resurfacing sizable defects of the pulp. METHODS: Flaps were designed on the lateral ulnar side of the middle finger for five thumb defects and the ring finger for two little finger defects. To provide sensation to the flap, one nerve fascicle from the direct small branches of the proper digital nerve after interfascicular dissection (palmar aspect of the flap) and the dorsal branch of the proper digital nerve (dorsal aspect) were identified and sectioned proximally, leaving a 1-cm nerve tail attached to the flap. RESULTS: These flaps provided sensate coverage with static two-point discrimination values of approximately 6 mm. Donor finger morbidity was minimal, and pulp sensation in donor fingers was normal in all cases. No donor finger cold intolerance was reported in this series. CONCLUSIONS: This described flap supplies glabrous skin of nearly normal sensibility. One nerve fascicle from the direct small branches of the proper digital nerve and the dorsal branch of the proper digital nerve were used for maximal sensation. Donor fingers are cosmetically better than those of dorsal middle phalangeal finger flaps because the grafted skin is hidden by an adjacent finger.

Adult↗

Diagnostic potential of three-dimensional ultrasound-based virtual cystoscopy: an experimental study using pig bladders.

OBJECTIVE: We sought to investigate the feasibility of 3-dimensional ultrasound (3D US)-based virtual cystoscopy in experimentally designed bladder phantoms using pig bladders. MATERIALS AND METHODS: Ten bladder phantoms with simulated polypoid tumors of different sizes were constructed to provide 3D US-based virtual cystoscopic images. The simulated polypoid tumors were divided by their location into 2 groups: group 1 included the polyps on the anterior and posterior walls, and group 2 included those on the remaining 4 walls. Two genitourinary radiologists independently interpreted the virtual cystoscopic images, with a consensus reached for cases with discrepant results. RESULTS: In a consensus reading, 3D US-based virtual cystoscopy detected 44 (91.7%) of 48 polypoid lesions. All lesions (n = 4) with false-negative results were 5 mm or smaller in diameter, and so the detection rate was 81.8% (18/22) for lesions 5 mm or smaller whereas it was 100% (26/26) for lesions larger than 5 mm. The detection rate for group 1 (93.8%) was not significantly different from that for group 2 (90.6%; P = 1.000). There were 7 false-positive lesions. Of these, 5 lesions were seen in group 1, and reverberation artifacts were the most common source of these errors (n = 4). Blind areas were present in 19 (31.7%) of 60 virtual cystoscopic images and were seen only in group 2. The differences in the false-positive rate and the incidence of blind area were statistically significant between both groups (P = 0.036, P = 0.00008, respectively). CONCLUSION: 3D US-based virtual cystoscopy may have diagnostic potential in the detection of polypoid bladder tumors.

Animals↗

Effect of cognitive training focusing on organizational strategies in patients with obsessive-compulsive disorder.

The purpose of the present paper was to develop a cognitive training program for patients with obsessive-compulsive disorder (OCD) and evaluate its effectiveness. Nine 60-min sessions focusing on the improvement of organizational strategies were given to 15 patients with OCD over a period of 5 weeks. The control group consisted of 15 age- and sex-matched patients also with OCD. The Rey-Osterrieth Complex Figure Test and Korean-California Verbal Learning Test were administered before and after cognitive training. Clinical symptoms were assessed with the Yale-Brown Obsessive-Compulsive Scale. The memory function in the treatment group improved and their clinical symptoms were alleviated after training, compared to those of the control group. Cognitive training of OCD patients not only improved their memory function, but also alleviated their clinical symptoms. Therefore, cognitive training, focusing on the improvement of organizational strategies, could be an effective treatment modality for patients with OCD.

Activities of Daily Living↗

Ulnar shortening osteotomy in idiopathic ulnar impaction syndrome. Surgical technique.

BACKGROUND: Idiopathic ulnar impaction syndrome can be defined as a degenerative condition of the ulnar aspect of the wrist in patients with congenital or dynamic positive ulnar variance without a history of fracture or premature physeal arrest. The purpose of this study was to evaluate the clinical features of idiopathic ulnar impaction syndrome and the outcomes of ulnar shortening osteotomy for this group of patients. METHODS: Thirty-one wrists in twenty-nine patients with idiopathic ulnar impaction syndrome were treated with an ulnar shortening osteotomy. Ulnar variance was measured on an anteroposterior radiograph of the wrist, and radioulnar distance was measured on a lateral radiograph, with the forearm in neutral rotation, to evaluate any displacement of the ulnar head from the distal aspect of the radius. All patients were followed clinically and radiographically for a mean of thirty-two months. RESULTS: An average preoperative ulnar variance of +4.6 mm (range, 2 to 7.5 mm) was reduced to an average of -0.7 mm (range, -4 to +1 mm) postoperatively. Preoperatively, the modified Gartland and Werley score was an average (and standard deviation) of 69.5 +/- 7.6, with twenty-four wrists rated poor and seven rated fair. Postoperatively, the score improved to an average of 92.5 +/- 8.0, with twenty-four wrists rated excellent; five, good; one, fair; and one, poor. Dorsal subluxation of the distal aspect of the ulna was found concomitantly in nine wrists, and it was found to be reduced by the shortening osteotomy. Seven patients had cystic changes in the carpal bones preoperatively, but these were not evident one to two years after the operation. CONCLUSIONS: Ulnar shortening osteotomy improved wrist function in patients with idiopathic ulnar impaction syndrome and reduced the subluxation of the distal radioulnar joint, which is commonly found in these patients. Degenerative cystic changes of the ulnar carpal bones appear to resolve following the shortening osteotomy.

Adolescent↗