Biomedical subjects

A Lindgren

Publications and source records attributed to A Lindgren.

At least 37 records · Page 2Linked to original sources

PubMed2001

Effect of interfering substances on current response of recombinant peroxidase and glucose oxidase-recombinant peroxidase modified graphite electrodes.

Graphite electrodes have been modified with different forms of horseradish peroxidase (HRP). These included native HRP, wild-type recombinant HRP, and two single-point recombinant HRP mutants, N70V and N70D. The mediator-less response of these electrodes to H2O2 was studied indicating that electrodes modified with recombinant HRP forms are more stable than those modified with native HRP. Various interfering compounds were investigated for their effect on the current response to H2O2. It was found that interferences such as acetaminophen and dopamine affected the response by mediating the electron transfer (ET) between graphite and peroxidases. The mediating behaviour manifested itself as an increased current of the electrode to H2O2. The interfering effect was less pronounced for the electrodes modified with recombinant HRPs possessing better electronic coupling with the graphite surface. The interfering behaviour of acetaminophen on the response for glucose with the bienzyme electrode containing co-immobilised glucose oxidase and HRP was mainly ascribed to mediation of ET between graphite and HRP. It was experimentally proven that a high efficiency of direct ET between graphite and recombinant HRP substantially reduces the interfering effect of acetaminophen.

Journal Article↗

PubMed2001

Pre-operative oestradiol levels - relation to survival in breast cancer.

AIMS: There are clinical observations that operation during the luteal phase of the menstrual cycle (with high oestradiol levels) may positively influence prognosis in breast cancer. However, few studies have information on plasma levels of hormones pre-operatively. METHODS: We studied 774 women treated for breast cancer where plasma levels of oestradiol had been measured 1-2 days pre-operatively. Date and cause of death were ascertained from the files of the Swedish Cancer Register and 5434 person-years were observed. The endpoint was death with breast cancer as the underlying cause (n=41 and n=158 in the pre- and post-menopausal group, respectively). RESULTS: In life-table analyses, only pre-menopausal patients with oestradiol 500 pmol/l and above had a tendency (not statistically significant) for better survival. Multivariate Cox models with oestradiol modelled in continuous form yielded relative hazards (RH) close to unity in all women and in strata according to menopausal status. CONCLUSIONS: When oestradiol was analysed in categorized form, only women with the highest levels had a tendency for improved prognosis (RH around 0.7; not statistically significant). Moreover, this pattern was not apparent for pre-menopausal women. Our findings contradict the notion that the pre-operative oestradiol level is independently associated with breast cancer prognosis.

Adult↗

PubMed2001

Vitamin B12 metabolism after urinary diversion with a Kock ileal reservoir.

OBJECTIVE: To elucidate the influence of construction of a Kock reservoir for urinary diversion using 70 cm of the distal ileum on vitamin B12 metabolism. MATERIAL AND METHODS: Blood samples for determination of cobalamin concentrations were drawn up to 18 years after construction of a Kock reservoir in 97 patients. Preoperative values were obtained in 20 of these patients. Pre- and postoperative Schilling tests and analyses of methylmalonic acid and homocysteine concentrations were performed in subgroups. RESULTS: The operation did not induce a significant decrease in cobalamin uptake as reflected in the pre- and postoperatively performed Schilling tests. No significant decline in cobalamin concentration postoperatively was noted. The value of analysis of methylmalonic acid and homocysteine concentrations in finding patients with cobalamin deficiency is limited by the fact that kidney function influences the results. Ten per cent of the patients did develop true cobalamin deficiency. A postoperative vitamin B12 value below 200 pmol/l indicates a 50% risk of later cobalamin deficiency. CONCLUSIONS: The construction of a Kock reservoir does not per se cause cobalamin deficiency. Substitution should be instituted at a postoperative concentration below 200 pmol/l.

Adult↗

PubMed2001

Diastolic blood pressure and area of residence: multilevel versus ecological analysis of social inequity.

STUDY OBJECTIVES: To study geographical differences in diastolic blood pressure and the influence of the social environment (census percentage of people with low educational achievement) on individual diastolic blood pressure level, after controlling for individual age and educational achievement. To compare the results of multilevel and ecological analyses. DESIGN: Cross sectional analysis performed by multilevel linear regression modelling, with women at the first level and urban areas at the second level, and by single level ecological regression using areas as the unit of analysis. SETTING: Malmö, Sweden (population 250 000). PARTICIPANTS: 15 569 women aged 45 to 73, residing in 17 urban areas, who took part in the Malmö Diet and Cancer Study (1991-1996). MAIN RESULTS: In the "fixed effects" multilevel analysis, low educational achievement at both individual (beta=1.093, SE=0.167) and area levels (beta=2.966, SE=1.250) were independently associated with blood pressure, although in the "random effects" multilevel analysis almost none of the total variability in blood pressure across persons was attributable to areas (intraclass correlation=0.3%). The ecological analysis also found an association between the area educational variable and mean diastolic blood pressure (beta=4.058, SE=1.345). CONCLUSIONS: The small intraclass correlation found indicated very marginal geographical differences and almost no influence of the urban area on individual blood pressure. However, these slight differences were enough to detect an effect of the social environment on blood pressure. The ecological study overestimated the associations found in the "fixed" effects multilevel analysis, and neither distinguished individual from area levels nor provided information on the intraclass correlation. Ecological analyses are inadequate to evaluate geographical differences in health.

Age Factors↗

PubMed2001

Cancer incidence in hypertensive patients in North Karelia, Finland.

Cancer incidence of 20 529 hypertensive patients included in the community-based hypertension register of the North Karelia Project was determined. A total of 2511 incident cancer cases were obtained among the patients in record linkage with the nationwide Finnish Cancer Registry during the mean follow-up time of 16 years. The age-adjusted incidence rates per 100 000 person-years were 248.4 for men and 171.7 for women, which correspond to that of the general population in the area. The Cox regression model was used to analyze the effect of hypertension-related variables on cancer incidence. In men, the diastolic blood pressure was associated with an increased cancer risk but only in those who smoked >10 cigarettes per day. The functional diagnosis of hypertension (stage I, hypertension with no end-organ damage; stage II, hypertension with left cardiac hypertrophy; and stage III, hypertension with extracardiac organ damage) was associated with the increased risk significantly in men who used antihypertensive drugs at baseline. In women, the diastolic blood pressure was associated with an increased cancer risk in those who did not use antihypertensive drugs at baseline. The functional diagnosis of hypertension was associated with an increased risk only in those who smoked >10 cigarettes per day, but the number of women and cancer cases in this group was small. These results indicate a complex pattern of diastolic blood pressure, functional diagnosis, use of antihypertensive drugs, smoking, and gender in the cancer risk of hypertensive patients.

Female↗

PubMed2001

Pure motor stroke from presumed lacunar infarct: long-term prognosis for survival and risk of recurrent stroke.

UNLABELLED: BACKGROUND AND PURPOSE A low risk of recurrent stroke and death after lacunar infarction has previously been reported, but follow-up has been limited to </=5 years. METHODS: One hundred eighty patients with pure motor stroke, collected between 1983 and 1986 from a hospital-based stroke registry, were followed up until at least 10 years after the index stroke. Two patients were lost to follow-up. Survival status was determined from the official population registry and compared with survival rates of the Swedish population, matched for age and sex. Cox proportional hazards regression analyses were used to identify independent prognostic predictors. RESULTS: During follow-up 106 (60%) of the 178 patients died, most commonly as a result of coronary heart disease. During the first 5 years after the stroke, survival rates were similar to those of the general population. Beyond this time the risk of death was increased among patients with pure motor stroke, with an excess of 10 to 15 percent units compared with the general population. Independent determinants for death were age (P<0.01), male sex (P<0.01), and nonuse of acetylsalicylic acid (P=0.02). Recurrent stroke occurred in 42 (23.5%) of the patients, corresponding to an annual risk of 2.4%. Hypertension (P=0.025) and diabetes (P=0.024) were independent risk factors for recurrent stroke. CONCLUSIONS: For the first few years after lacunar infarct, the risk of death was similar to that of the general population, but later a clear excess of death was observed. The long-term prognosis in lacunar infarction appears less favorable than previously reported.

Adult↗

PubMed2001

Management and prognostic features of intracerebral hemorrhage during anticoagulant therapy: a Swedish multicenter study.

BACKGROUND AND PURPOSE: Patients treated with oral anticoagulants (ACs) have an increased risk of intracerebral hemorrhage (ICH), which is more often fatal than spontaneous ICH. Options to reverse the AC effect include intravenous administration of vitamin K, plasma, and coagulation factor concentrate. However, the optimal management of AC-related ICH has not been determined in any randomized trial. In this study, the present management of AC-related ICH was surveyed, and determinants of survival were assessed. METHODS: We retrospectively reviewed the medical records of all AC-related ICHs at 10 Swedish hospitals during a 4-year period, 1993 to 1996. Survival status after the ICH was determined from the Swedish National population register. RESULTS: We identified 151 patients with AC-related ICH. Death rates were 53.6% at 30 days, 63.6% at 6 months, and 77.5% at follow-up (mean 3.5 years). The case fatality ratio at 30 days was 96% among patients unconscious on admission (n=27), 80% among patients who became unconscious before active treatment was started (n=15), 55% among patients in whom no special action was taken except withdrawal of AC treatment (n=42), and 28% among patients given active anti-coumarin treatment while they were still conscious (n=64). The case fatality ratio at 30 days was 11% in the group treated with plasma (n=18), 30% in the group treated with vitamin K (n=23), and 39% in the group treated with coagulation factor concentrate (n=23). Within the first 24 to 48 hours after admission, 47% of the patients deteriorated. Choice of therapy to reverse the AC effect differed substantially between the hospitals (P<0.0001), as did the time interval from symptom onset to start of treatment. Multiple logistic regression analysis showed only 2 factors (intraventricular extension of bleeding and ICH volume) that were independently related to case fatality at both 30 days and 6 months. The results were similar when the analysis was restricted to patients who were conscious on admission. CONCLUSIONS: In AC-related ICH, a progressive neurological deterioration during the first 24 to 48 hours after admission is frequent, and the mortality is high. Choice of therapy to reverse the AC effect differed considerably between the hospitals. There was no evidence that any treatment strategy was superior to the others. A randomized controlled trial is needed to determine the best choice of treatment.

Adult↗

PubMed2001

Hyperhomocysteinemia and changed plasma thiol redox status in chronic obstructive pulmonary disease.

Reduced and total homocysteine, cysteine, glutathione and cysteinylglycine in plasma were investigated in 19 patients with chronic obstructive pulmonary disease and in 29 healthy subjects. The purpose was to examine the influence of pro-oxidant activity caused by the lung disease on the metabolism of homocysteine and other plasma thiols. We observed a decreased concentration of reduced glutathione and a decreased ratio of reduced/total glutathione in the patients compared to the healthy individuals, which supports the hypothesis of an association between free radicals and pathogenesis in some lung diseases. We also observed an increased total plasma homocysteine. The influence of a possible extracellular pro-oxidant activity on the concentration of total plasma homocysteine is discussed.

Aged↗

PubMed2001

Perfusion-related parameters in intravoxel incoherent motion MR imaging compared with CBV and CBF measured by dynamic susceptibility-contrast MR technique.

OBJECTIVE: Perfusion-related parameters obtained by intravoxel incoherent motion (IVIM) MR imaging (MRI) were compared with cerebral blood volume and flow (CBV and CBF), retrieved by dynamic susceptibility-contrast (DSC) MRI. MATERIAL AND METHODS: Twenty-eight volunteers (average age 68.5 years) were investigated. Spin-echo echo-planar imaging with IVIM-encoding gradients was employed (36 different b values, 0-1200 s/mm2). The perfusion fraction and the pseudo-diffusion coefficient were calculated for regions in thalamus gray matter and frontal white matter, using asymptotic and full fitting. In DSC-MRI, a Gd-DTPA-BMA contrast-agent bolus was monitored using simultaneous-dual FLASH. Deconvolution of the measured tissue concentration-versus-time curve with an arterial input function from the carotid artery was applied, and maps of CBV and CBF were calculated. RESULTS: The correlation between the perfusion fraction and CBV was r=0.56 (p<0.0000006) using asymptotic fitting, and r=0.35 (p<0.0004) when full fitting was applied. Average CBF was 41.5 ml/(min 100 g), to be compared with the IVIM-based value of 63.6 ml/(min 100 g), obtained from the median value of the pseudo-diffusion coefficient in combination with assumptions about capillary network structure. CONCLUSION: The IVIM concept provided results that agreed reasonably with conventional CBV and CBF. The non-linear fitting to noisy signal data was problematic, in accordance with previously presented simulations.

Aged↗

PubMed2000

The pachytene checkpoint in Saccharomyces cerevisiae requires the Sum1 transcriptional repressor.

Saccharomyces cerevisiae mutants that fail to complete meiotic recombination are blocked by the RAD17/RAD24/MEC1 checkpoint signaling pathway in pachytene when early sporulation genes are expressed. Middle genes are not activated in checkpoint-arrested cells because the Ndt80 transcription factor is inhibited. We find that the pachytene checkpoint requires Sum1, a transcriptional repressor that recognizes a subset of Ndt80-binding sites. Mutants lacking Sum1 or Rad17 partially bypass the block to the nuclear divisions but do not form spores, while mutants lacking both Sum1 and Rad17 completely bypass the block and form morphologically normal spores. The level of Sum1 protein decreases as middle genes are expressed, and this decrease is blocked in checkpoint-arrested cells. These data suggest that Sum1 levels are regulated by the checkpoint and that progression of the meiotic divisions and spore differentiation can be differentially controlled by competition of the Sum1 repressor and Ndt80 activator for occupancy at key middle promoters.

Blotting, Northern↗

PubMed2000

[Evaluation of analytic test methods. Stomach-intestines status is the best diagnostic method in suspected vitamin B12 deficiency].

In the great majority of cases vitamin B12 deficiency is caused by chronic atrophic gastritis. This study has compared several different tests for the identification of patients for whom substitution therapy is needed or warranted. It is concluded that serum tests reflecting the state of the gastric body mucosa (serum pepsinogen A combined with serum gastrin or serum pepsinogen C) appear to be the logical first step in the workup of these patients in terms of high sensitivity and superior specificity as compared with other tests.

Biomarkers↗

PubMed2000

Anisotropic orientation of horseradish peroxidase by reconstitution on a thiol-modified gold electrode.

Horseradish peroxidase (HRP) was reconstituted on the surface of a gold electrode that was modified first with a hemin-carbon-chain-thiol derivative followed by addition of the apo protein to the contacting solution. To facilitate the reconstitution of the holo enzyme, the hemin needs to be immobilised on a carbon-chain spacer arm. To achieve this, an immobilisation protocol was developed that is based on the initial formation of a mixed self-assembled monolayer on the gold surface consisting of 3-carboxypropyl disulphide and an activated disulphide (3,3'-dithiodipropionic acid di-(N-succinimidyl ester)) followed by binding of a diaminoalkane to the activated disulphide. The hemin was then coupled to the second amino group of the diaminoalkane by means of a carbodiimide coupling reagent. Finally, the enzyme was reconstituted on the hemin-modified surface by immersion of the electrode in a solution containing apo-HRP. The advantage of this method is that the length of the spacer arm can be changed easily, because diaminoalkanes of different chain lengths are available. The electrochemistry of the hemin and the reconstituted HRP electrodes was studied by means of cyclic voltammetry and differential-pulse voltammetry. The catalytic ability for reduction of hydrogen peroxide was investigated for both direct and mediated electrochemistry with a soluble electron donor (ortho-phenylenediamine).

Electrochemistry↗

PubMed2000

The role of tobacco, snuff and alcohol use in the aetiology of cancer of the oesophagus and gastric cardia.

While tobacco and alcohol are established risk factors for oesophageal squamous-cell carcinoma, their roles in the aetiology of the increasingly common oesophageal adenocarcinoma remains uncertain. We tested the association between tobacco, snuff and alcohol use and the risk of oesophageal and cardia cancer in a nationwide, population-based case-control study in Sweden. Face-to-face interviews were conducted with 618 (81% of all eligible) patients (189 oesophageal adenocarcinoma, 262 cardia adenocarcinoma and 167 oesophageal squamous-cell carcinoma) and 820 control subjects. Odds ratios (OR) were calculated by logistic regression with multivariate adjustments for potential confounding. The risk of oesophageal adenocarcinoma was not associated with snuff or alcohol use, and the association with smoking was weak or absent. Gastric cardia adenocarcinoma was dose-dependently associated with smoking (OR=4.2, 95% CI=2.5-7.0 among heavy smokers compared with never-smokers), but not with alcohol or snuff use. Oesophageal squamous-cell carcinoma was strongly associated with tobacco, moderately with alcohol, but not with snuff use; combined use of tobacco and alcohol entailed a strongly increased risk (OR=23.1, 95% CI=9.6-56.0 among heavy users compared with never-users). We conclude that tobacco smoking, a strong risk factor for oesophageal squamous-cell carcinoma and cardia adenocarcinoma, does not play an important role in the aetiology of oesophageal adenocarcinoma. None of the studied exposures can explain the increasing incidence of oesophageal adenocarcinoma.

Adenocarcinoma↗

PubMed2000

Assessment of regional cerebral blood flow by dynamic susceptibility contrast MRI using different deconvolution techniques.

Regional cerebral blood flow (rCBF) was assessed using dynamic susceptibility-contrast MRI at 1.5 T. A simultaneous dual FLASH pulse sequence and Gd-DTPA-BMA (0.3 mmol/kg b.w.) were used for examination of 43 volunteers, measuring rCBF in frontal white matter (WM) and in gray matter in the thalamus (GM). Arterial input functions (AIFs) were registered 1) in the carotid artery and 2) in an artery within the GM/WM slice. The measured concentration-vs. -time curve was deconvolved with the AIF using both Fourier Transform (FT) and Singular Value Decomposition (SVD). Relative rCBF was given by the height of the deconvolved response curve. For each volunteer, eight different rCBF maps were calculated, representing different combinations of deconvolution techniques, AIFs, and filters. The average GM-WM rCBF ratios ranged from 2.0-2.2, depending on methodology. Absolute rCBF was 68 +/- 28 ml/(min 100 g) in GM and 35 +/- 13 ml/(min 100g) in WM (mean +/- SD, n = 39). GM-WM rCBF ratios obtained using SVD were 6-10% higher than corresponding ratios obtained using FT.

Adult↗

PubMed2000

Absolute cerebral blood flow measured by dynamic susceptibility contrast MRI: a direct comparison with Xe-133 SPECT.

Absolute regional cerebral blood flow (CBF) was measured in ten healthy volunteers, using both dynamic susceptibility-contrast (DSC) magnetic resonance imaging (MRI) and Xe-133 SPECT within 4 h. After i.v. injection of Gd-DTPA-BMA (0.3 mmol/kg b.w.), the bolus was monitored with a Simultaneous Dual FLASH pulse sequence (1.5 s/image), providing one slice through brain tissue and a second slice through the carotid artery. Concentration C(t) is proportional to -(1/TE) ln[S(t)/S(0)] was related to CBF as C(t) = CBF [AIF(t) x R(t)], where AIF is the arterial input function and R(t) is the residue function. A singular-value-decomposition-based deconvolution technique was used for retrieval of R(t). Absolute CBF was given by Zierler's area-to-height relation and the central volume principle. For elimination of large vessels (ELV), all MRI-based CBF values exceeding 2.5 times the mean CBF value of the slice were excluded. A correction for partial-volume effects (CPVE) in the artery used for AIF monitoring was based on registration of signal in a phantom with tubes of various diameters (1.5-6.5 mm), providing an individual concentration correction factor applied to AIF data registered in vivo. In the Xe-133 SPECT investigation, 3,000-4,000 MBq of Xe-133 was administered intravenously, and CBF was calculated using the Kanno Lassen algorithm. When ELV and CPVE were applied, DSC-MRI showed average CBF values from the entire slice of 43 +/- 10 ml/(min 100 g) (small-artery AIF) and 48 +/- 17 ml/(min 100 g) (carotid-artery AIF) (mean +/- S.D., n = 10). The corresponding Xe-133-SPECT-based CBF was 33 +/- 6 ml/(min 100 g) (n = 10). The relationships of CBF(MRI) versus CBF(SPECT) showed good linear correlation (r = 0.74-0.83).

Aged↗

PubMed2000

Redox status of plasma homocysteine and other plasma thiols in stroke patients.

Despite the growing evidence that plasma homocysteine is a cardiovascular risk factor, the mechanism behind the vascular injuries is still unknown. Studies are difficult as a result of the fact that little is known about the formation of different homocysteine species in vivo. Since extracellular glutathione and cysteine may influence the formation of different homocysteine species, we have in the present study investigated the different fractions of homocysteine and their relation to the different fractions of glutathione and cysteine in stroke patients and control subjects. We found a ratio of about 32-33% between reduced and total plasma glutathione concentrations and 2.6 3.0% between reduced and total plasma cysteine concentrations both in patients and in healthy control subjects. We noted an elevated concentration of total plasma homocysteine in stroke patients, but no difference in the ratio between reduced and total plasma homocysteine concentrations in patients and control subjects (mean value 1.20 and 1.10%, respectively). However, in a subgroup of patients with higher concentrations of total plasma homocysteine, we observed a significantly lower ratio of reduced to total plasma homocysteine compared to a subgroup of patients with lower concentration of total plasma homocysteine. A low reduced/total ratio of plasma homocysteine in combination with elevated plasma homocysteine concentrations might reflect an increased pro-oxidant activity in plasma from these patients. Thus, increased pro-oxidant activity in plasma might be one factor, besides genetic and nutritional factors, that could explain hyperhomocysteinemia. Since substantial evidence indicates that progression of atherosclerosis is related to enhanced pro-oxidant activity, the premature vascular disease associated with increased plasma homocysteine concentration might be as a result of increased pro-oxidant activity and the elevated plasma homocysteine concentration may only reflect the increased oxidative stress.

Aged↗

PubMed2000

Biosensors based on novel peroxidases with improved properties in direct and mediated electron transfer.

Native horseradish peroxidase (HRP) on graphite has revealed approximately 50% of the active enzyme molecules to be in direct electron transfer (ET) contact with the electrode surface. Some novel plant peroxidases from tobacco, peanut and sweet potato were kinetically characterised on graphite in order to find promising candidates for biosensor applications and to understand the nature of the direct ET in the case of plant peroxidases. From measurements of the mediated and mediatorless currents of hydrogen peroxide reduction at the peroxidase-modified rotating disk electrodes (RDE), it was concluded that the fraction of enzyme molecules in direct ET varies substantially for the different plant peroxidases. It was observed that the anionic peroxidases (from sweet potato and tobacco) demonstrated a higher percentage of molecules in direct ET than the cationic ones (HRP and peanut peroxidase). The peroxidases with a high degree of glycosylation demonstrated a lower percentage of molecules in direct ET. It could, thus, be concluded that glycosylation of the peroxidases hinders direct ET and that a net negative charge on the peroxidase (low pI value) is beneficial for direct ET. Especially noticeable are the values obtained for sweet potato peroxidase (SPP), revealing both a high percentage in direct ET and a high rate constant of direct ET. The peroxidase electrodes were used for determination of hydrogen peroxide in RDE mode (mediatorless). SPP gave the lowest detection limit (40 nM) followed by HRP and peanut peroxidase.

Arachis↗

PubMed2000

Body size in different periods of life, diabetes mellitus, hypertension, and risk of postmenopausal endometrial cancer (Sweden).

OBJECTIVE: To measure the association between endometrial cancer risk and obesity at age 18 and recently, adult weight gain, diabetes mellitus and hypertension. METHODS: We performed a population-based, nationwide case-control study among postmenopausal women aged 50-74 years in Sweden, including 709 incident cases with histopathologically verified endometrial cancer and 3368 controls. RESULTS: Compared to lean women (recent body mass index (BMI), i.e. kg/m2 below 22.5), overweight women (recent BMI 28-29.99) had a 50% increase in risk for endometrial cancer (OR 1.5, 95% CI 1.0-2.1). Obese women (recent BMI 30-33.99) had a 3-fold increased risk (OR 2.9, 95% CI 2.0-4.0), and markedly obese women (recent BMI > or = 34) a 6-fold increased risk (OR 6.3, 95% CI 4.2-9.5). The OR for Type 2 diabetes mellitus was 1.5 (95% CI 1.0-2.1) and for Type 1 diabetes mellitus it was 13.3 (3.1-56.4). The effect of recent BMI was similar for tumors having different degrees of differentiation and myometrial invasion, and did not vary with age, time since menopause, smoking status, diabetes mellitus, and use of contraceptives. Hypertension increased risk only among obese women. BMI at age 18, height, and adult weight change were not independent risk factors. CONCLUSIONS: Recent overweight/obesity and diabetes mellitus (Types 1 and 2) are associated with endometrial cancer risk. Hypertension increases risk among obese women.

Adolescent↗