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Biomedical subjects

N Ahmed

Publications and source records attributed to N Ahmed.

At least 55 records · Page 3Linked to original sources
PubMed2003

Delay in migration of the corneal epithelium after incorporation of [3H]-mannose in organ cultures.

PURPOSE: Corneal epithelial cell surface carbohydrate moieties influence migration during wound healing. The purpose of the present study was to investigate the incorporation of galactose and mannose sugar during corneal epithelial migration and their effect on the rate of wound healing. METHODS: Organ cultures of non-migrating (n = 6) and migrating (n = 30) corneal epithelia were prepared. The incorporation of [3H]-galactose and [3H]-mannose was followed in the migrating samples after 18, 24, 48 and 72h incubation and at 18h in the non-migrating samples. Wound size was documented at the same intervals and the rate of healing was established. RESULTS: The migrating corneal epithelium of the galactose and mannose treated samples incorporated more radioactive sugar than the non-migrating samples. Mannose incorporation decreased with time whereas the rate of healing was significantly delayed (41 +/- 0.01 microm/h) compared to galactose treated samples (63 +/- 0.01 microm/h) and controls (61 +/- 0.01 microm/h) during the active healing phase (18-48h). Galactose incorporation increased with time. CONCLUSIONS: Incorporation of mannose sugar has an inhibitory effect on the rate of migration during the linear healing phase of the corneal epithelium.

Animals↗
PubMed2003

A systematic review of the adjunctive use of systemic corticosteroids for pulmonary tuberculosis.

OBJECTIVE: To determine the safety and benefit of adjunctive systemic corticosteroid therapy in the management of pulmonary tuberculosis. METHODS: A systematic review of 11 randomized, comparative clinical trials published from 1959 to 1999 involving the use of prednisone, prednisolone and/or adrenocorticotrophin (ACTH) in conjunction with standard anti-tuberculosis chemotherapy. A total of 1814 steroid-treated patients were analyzed, most of whom had moderate to severe disease and cavitation. Clinical, microbiologic and radiographic outcome measures included time to defervescence, weight gain, normalization of serum albumin level and erythrocyte sedimentation rate, length of hospitalization, rate and rapidity of sputum conversion and radiographic regression of pulmonary infiltrates and cavities. RESULTS: Corticosteroid therapy resulted in broad and significant clinical benefits in almost all of the studies reviewed. More rapid radiographic resolution of pulmonary infiltrates and, to a lesser extent, closure of cavities accompanied steroid use, especially in the first 4 months, but extended up to one year after initiation of treatment. Steroids did not have any appreciable effect on the speed or rate of sputum conversion. No detrimental side-effects attributed to steroid therapy or bacteriologic relapse were observed. CONCLUSION: The adjunctive use of systemic corticosteroid therapy can safely provide significant early and prolonged clinical and radiographic benefits in selected patients with advanced pulmonary tuberculosis.

Adrenocorticotropic Hormone↗
PubMed2003

Ischemic stroke subtypes in Pakistan: the Aga Khan University Stroke Data Bank.

OBJECTIVE: Frequency of ischemic stroke subtypes is influenced by ethnic and geographic variables. Our objective was to identify various stroke subtypes and its determinants at a tertiary care hospital. METHODS: We prospectively collected data on ischemic stroke subtypes admitted to The Aga Khan University Hospital in Karachi. RESULTS: A total of 596 patients were enrolled in 22 months in the Aga Khan Universtiy Stroke Registry. These included 393 patients with Ischemic stroke, 126 patients with intracerebral hemorrhage, 50 patients with subarachnoid hemorrhage and others. The ischemic stroke group was classified according to the TOAST criteria and comprised of lacunar 168/393 (42.7%); large artery atherosclerosis 106/393 (26.9%); cardioembolic 24/393 (6.1%); undetermined 80/393 (20.3%); and other determined types 15/393 (3.8%). The high proportion of lacunar strokes in our population may be due to high burden of inadequately treated hypertension and diabetes. Clear cut cardioembolic stroke was relatively infrequent in our population. CONCLUSION: Lacunar stroke is the most common subtype of stroke in our patient population. This is most likely secondary to uncontrolled hypertension.

Adult↗
PubMed2003

HLA-matching by DNA methods: impact on a living related renal transplantation programme.

DNA methods have resulted in improved renal allograft survival rates in cadaveric renal transplantation. This paper describes the impact of DNA typing by PCRSSP on a living related renal transplant (LRRT) programme. It evaluates error rates in serology, acute rejections, graft function and survival rates between the two typing methods. Serological typing was done on CTS 120 antisera Class 1 and 60 antisera Class 2 and 72 antisera Terasaki Class1 and 72 antisera Class2 Antigens. Low resolution PCR-SSP typing was done by 24 primers for HLA A , 48 for HLA B and 24 for HLA DR. Of the 585 transplants, 159 (Group I) were serology based, 172 serology and PCR-SSP for HLA DR (Group II) and 254 on serology and PCR-SSP for HLA A and B and only PCR-SSP for HLA DR (Group III). Error rates in serology as compared to PCR-SSP were 24% for HLA A, 16% for HLA B and 35% for HLA DR. Acute rejection in Group I were 39% Group II 30% and Group III 26% (p 0.02). Graft function of serum creatinine<1.5 mg/dl at 1 year was found in 26% of Group I patients as compared to 48% of Group III (p<0.0001). One and three year graft survival was 93% and 87% for Group II as compared to 81% and 69% for Group I respectively (p 0.0001). Matching by this combination of serology and PCR-SSP is not only economical for a developing country but also improves graft survival by 12% at 1 and 18% at 3 years.

Acute Disease↗
PubMed2002

Increased serum levels of vascular endothelial growth factor correlate with splenomegaly in polycythemia vera.

Angiogenesis has been implicated in the growth, dissemination and metastasis of solid tumours. Several recent studies have shown increased bone marrow vasculature in acute and chronic leukaemia as well as in myelofibrosis and myelodysplastic syndromes. Increased serum and/or cellular levels of vascular endothelial growth factor (VEGF) as the most potent and specific angiogenic factor were reported in acute and chronic leukaemia and multiple myeloma and also predict poor prognosis in these haematological malignancies. Little is known about angiogenesis and VEGF levels in polycythemia. Thus, the serum levels of VEGF (pg/ml) and erythropoietin (U/l) were determined using ultra-sensitive ELISA assays in 16 polycythemia patients (10 with polycythemia vera (PV) and 6 with secondary polycythemia) and correlated with their clinical and laboratory features. The serum levels of VEGF were significantly higher in 90% of PV cases and 60% of secondary polycythemia compared to healthy controls. The median VEGF levels (pg/ml) were 622 (range, 272-4760), 306 (range, 111-408) and 143 (range, 91-282) in PV, secondary polycythemia and healthy controls, respectively. Since serum VEGF reflects both plasma VEGF and platelet released VEGF, the concentration of VEGF per platelet (VEGF/PLT) as pg per 10(6) platelet was used as a more standardised measure. Splenomegaly emerged as the main factor associated with a marked increase in serum VEGF/PLT levels. On the other hand, the serum erythropoietin levels (U/l) were significantly reduced in PV (range, 1.2-14.3) raised in secondary polycythemia (range, 26-104) compared with normal controls (range, 9.7-31.1), P<0.01. In conclusion, the present study shows increased VEGF levels in most polycythemia patients, and splenomegaly is associated with a profound increase in VEGF serum levels in these patients. Also, patients with PV have significantly reduced serum levels of erythropoietin compared with secondary polycythemia. Also, serum VEGF/PLT was higher in PV patients treated with phlebotomy alone rather than oral chemotherapy, suggesting a possible advantage for chemotherapy over phlebotomy alone in suppressing the disease progression. Further studies with large number of polycythemia cases are warranted to explore the role of these cytokines in the pathogenesis, diagnosis and/or therapy of polycythemia.

Adult↗
PubMed2002

Chronic myeloid leukemia and acromegaly in POEMS syndrome.

We describe an acromegalic patient who has developed both chronic myeloid leukemia (CML) and a plasma cell dyscrasia. However, as the patient also has neuropathy, hyperhydrosis and other endocrine disorders, he appears to have an atypical form of POEMS syndrome.

Acromegaly↗
PubMed2002

Epilepsy and injury mortality in Sweden--the importance of changes in coding practice.

We analysed national mortality trends of injuries and poisoning in patients with epilepsy to establish the importance of changes in coding practice. Patients where epilepsy was a syndrome, either as an underlying or contributing cause-of-death at any time of life, throughout Sweden during 1975-1995 were included. All conditions mentioned on each death certificate were examined, and epilepsy and injury diagnoses were separated according to underlying, contributing or multiple cause-of-death. Annual mortality rates, case-fatality rates, and linear regression coefficients were computed. The most common underlying cause-of-death (UCD) was diseases of the circulatory system (34.4%) followed by epilepsy (31.7%). Injury and poisoning were coded as UCDs for 5.8% of the patients. Injury and poisoning as a contributory cause-of-death increased significantly, but not as an underlying cause during the study period. The proportion of each diagnostic group as an underlying cause decreased by 35% for epilepsy and 18% for injury from 1981 and onwards. These changes should be interpreted with caution since changes of coding practice are more likely to be the cause of these apparent changes. The most frequent specific external causes of injury deaths in epileptic patients were falls and drowning. Intracranial fatal injuries in connection with fall accidents predominated, especially among elderly persons. Deaths related to accidental poisoning were caused by the toxic effect of non-medicinal substances. Cause-of-death statistics from different countries must be interpreted with caution when making international comparisons. Both underlying and contributing cause-of-death statistics should be considered in analyses of mortality trends.

Adolescent↗
PubMed2002

Reduction of Cr(VI) and bioaccumulation of chromium by gram positive and gram negative microorganisms not previously exposed to Cr-stress.

Resistance to Cr(VI) is usually associated with its cellular exclusion, precluding enrichment techniques for the isolation of organisms accumulating Cr(VI) via bioreduction to insoluble Cr(III). A technique was developed to screen for potential Cr(VI) reduction in approx. 2000 isolates from a coastal environment, based on the non-specific reduction of selenite and tellurite to Se0 and Te0, and reduction of tetrazolium blue to insoluble blue formazan. The most promising strains were further screened in liquid culture, giving three, which were identified by 16S rRNA sequence analysis as Bacillus pumilus, Exiguobacterium aurantiacum and Pseudomonas synxantha, all of which reduced 100 microM Cr(VI) anaerobically, without growth. The respective removal of Cr(VI) was 90% and 80% by B. pumilus and E. aurantiacum after 48 h and 80% and by P. synxantha after 192 h. With the gram positive strains Cr(VI) promoted loss of flagella and, in the case of B. pumilus, lysis of some cells, but Cr was deposited as an exocellular precipitate which was identified as containing Cr and P using energy dispersive X-ray microanalysis (EDAX). This prompted the testing of Citrobacter sp. N14 (subsequently re-assigned by 16S rRNA sequence analysis and biochemical studies as a strain of Serratia) which bioprecipitates metal cation phosphates via enzymatically-liberated phosphate. This strain reduced Cr(VI) at a rate comparable to that of P. synxantha but Cr(III) was not bioprecipitated where La(III) was removed as LaPO4, even though a similar amount of phosphate was produced in the presence of Cr(III). Since B. pumilus removed most of the Cr(VI), with the formation of cell-bound CrPO4 implicated, this suggests that this strain could have future bioprocess potential.

Bacillus↗
PubMed2002

Overexpression of alpha(v)beta6 integrin in serous epithelial ovarian cancer regulates extracellular matrix degradation via the plasminogen activation cascade.

Recent evidence suggests that integrins are involved in the multi-step process of tumour metastasis. The biological relevance of alpha(v) integrins and associated beta-subunits in ovarian cancer metastasis was examined by analysing the expression of these cell surface receptors in nine ovarian cancer cell lines and also in the primary human ovarian surface epithelial cell line (HOSE). beta1, beta3 and beta5 subunits were present in all ten ovarian cell lines. beta6 subunit was present at varying levels in eight out of nine cancer cell lines but was absent in the HOSE cell line. Immunohistochemical staining showed that beta6 was present in both non-invasive (borderline) and high-grade ovarian cancer tissues but was absent in benign and normal ovarian tissue. High alpha(v)beta6 integrin expressing ovarian cancer cell lines had high cell surface expression of uPA and uPAR. Ovarian cancer cell lines expressing high to moderate level of alpha(v)beta6 integrin demonstrated ligand-independent enhanced levels of high molecular weight (HMW)-uPA and pro-matrix metalloproteinase 2 and 9 (pro-MMP-2 and pro-MMP-9) expression in the tumour-conditioned medium. High and moderate expression of alpha(v)beta6 integrin correlated with increased plasminogen-dependent degradation of extracellular matrix which could be inhibited by inhibitors of plasmin, uPA and MMPs or by monoclonal antibody against uPA, MMP-9 or alpha(v)beta6 integrin. These results suggest that endogenous de novo expression of alpha(v)beta6 integrin in ovarian cancer cells may contribute to their invasive potential, and that alpha(v)beta6 expression may play a role in ovarian cancer progression and metastasis.

Antigens, Neoplasm↗
PubMed2002

The prothrombin G20210A polymorphism in patients with myocardial infarction.

To investigate a possible association between the human prothrombin gene G20210A polymorphism and coronary artery thrombosis, we screened 172 consecutive patients with ischaemic heart disease admitted for coronary arteriography. The patients were divided into two groups on the basis of their clinical history and examination of their hospital records: 66 patients with a definite previous myocardial infarction, and 106 with angina-like chest pain but no evidence of myocardial infarction. The overall frequency of the G20210A polymorphism was 0.011, four out of the 172 patients being heterozygous for the mutation. The allelic frequency was 0.015 in the group with myocardial infarction and 0.009 in the group without myocardial infarction (P = 0.622). The results of this study suggest that the single nucleotide polymorphism at position 20210 of the prothrombin gene is unlikely to be a risk factor for coronary thrombosis.

Adult↗
PubMed2002

Platelet membrane glycoprotein Ibalpha gene -5T/C Kozak sequence polymorphism as an independent risk factor for the occurrence of coronary thrombosis.

OBJECTIVE: To explore the potential of the GPIbalpha gene variable number tandem repeat (VNTR) and -5T/C Kozak polymorphisms to act as independent risk factors for myocardial infarction. METHODS: 256 patients aged 33-80 years (180 caucasian, 76 Indian Asian) were recruited at cardiac catheterisation for any diagnostic indication, and divided into two groups: group A, with confirmed previous myocardial infarction evident on ECG or ventriculogram (88 patients, 79 men, 9 women) and group B, with no evidence of myocardial infarction (168 patients, 101 men, 67 women). RESULTS: There was no significant difference in race, age, hypertension, smoking status, or family history between the infarct and non-infarct groups, though there was a significant difference in sex (89.8% male in group A, 60.1% male in group B, p < 0.001). Genotype analysis showed a strong association between the GPIbalpha Kozak homozygous TT genotype and the occurrence of myocardial infarction (group A: TT 85.2%, TC 12.5%, CC 2.3%; group B: TT 67.3%, TC 32.7%, p = 0.001). No significant association was found between myocardial infarction and the GPIbalpha VNTR, although analysis of the CC VNTR genotype against all other GPIbalpha VNTR genotypes showed a marginal association with myocardial infarction (p = 0.059). There was no association between the Kozak sequence polymorphism (p = 0.797) or GPIbalpha VNTR (p = 0.714) and the degree of vessel disease. CONCLUSIONS: The homozygous TT Kozak genotype may be a significant factor in the outcome of coronary artery disease completed by myocardial infarction. Conversely, the Kozak C allele in the heterozygous state TC may confer some protection against myocardial infarction.

Adult↗
PubMed2002

Role of dexamethasone in acute bacterial meningitis in adults.

OBJECTIVE: To evaluate the role of dexamethasone as adjunctive therapy in adult acute bacterial meningitis (ABM) in two groups of patients treated with antibiotics alone or a combination of antibiotics and dexamethasone. DESIGN: Systematic sampling interventional open cohort study. SETTING: Department of Medicine (Medical Unit II), Jinnah Postgraduate Medical Centre, Karachi. PATIENTS: Sixty eight patients aged 12-85 years admitted in Medical Unit II and diagnosed to have ABM. Patients were divided into two groups. Group A received anti-microbial therapy for 14 days (a combination of benzyl penicillin 6 million units I/V 6 hourly and chloramphenicol 1 gm I/V 6 hourly) and group B received the same antimicrobial therapy with dexamethasone 0.6 mg/kg/day in 3 divided doses for 4 days. MAIN OUTCOME MEASURES: Differences in mortality and morbidity in the two groups and differences in the CSF inflammatory parameters between the two groups of patients. RESULTS: There was early resolution of fever, headache and altered consciousness in group B as compared to group A. Cranial nerves involvement was lower in group B. There was no difference in the occurrence of other focal neurological deficits between the two groups. CSF inflammatory parameters (glucose, protein and WBC count) were significantly better in group B by day 5. No complications attributable to dexamethasone were seen in group B. CONCLUSION: There was early resolution of symptoms and CSF inflammatory parameters in the group that received dexamethasone as adjuvant therapy. Mortality was lower in the group treated with dexamethasone but the difference was not statistically significant. Dexamethasone should be administered to all adults patients with ABM.

Adolescent↗
PubMed2002

Amoebic versus pyogenic liver abscess.

OBJECTIVES: To study the differences between the clinical presentation and complications of amoebic and pyogenic liver abscess. To correlate the diagnostic significance of Entamoeba Indirect Haemagglutination test (E.IHA) in establishing the diagnosis of amoebic liver abscess. DESIGN: Open cohort observational study. SETTING: Department of Medicine (Medical Unit II) Jinnah Postgraduate Medical Centre, Karachi. PARTICIPANTS: Fifty two patients aged 13-70 years admitted in Medical Unit II and diagnosed to have liver abscess. INTERVENTIONS: Group A comprised of patients clinically diagnosed to have amoebic liver abscess and received Metronidazole 500mg iv x 8 hourly for atleast 10 days or more if patient developed complications. Group B comprised of patients diagnosed to have pyogenic abscess and received Cefotaxime 1g iv x 8 hourly for the same duration or more if complicated (antibiotic reviewed in accordance with culture and sensitivity report). MAIN OUTCOME MEASURES: Differences in the clinical presentation, complications and diagnostic parameters between the two groups of patients. RESULTS: It was not possible to differentiate between amoebic and pyogenic liver abscess on clinical grounds, routine investigations and imaging techniques. Aspiration of pus, especially if the abscess was multiple, was most helpful in differentiating the two types of abscesses. Serological test of E.IHA was highly specific and sensitive for amoebic liver abscess. CONCLUSION: Majority of liver abscesses in Karachi are due to Entamoeba Histolytica. Pyogenic abscess though less frequent, must be excluded by pus aspiration and culture and sensitivity. E.IHA is a good rapid method of discriminating between the two types of abscesses.

Adolescent↗
PubMed2001

L-tryptophan attenuation of the dopaminergic and behavioral responses to cocaine.

This study assessed the effects of acute intravenous L-tryptophan (neutral amino acid precursor for serotonin) administration on cocaine-induced dopaminergic responses. Male Sprague-Dawley rats were surgically implanted with guide cannulas in the nucleus accumbens 5 days prior to the study and with vascular catheters (carotid artery and jugular vein) on the day prior to the study. Using microdialysis, extracellular nucleus accumbens dopamine levels were measured in freely moving rats. Following a 2 h equilibration period, animals were randomized (n=7-8 per group) to receive either a constant intravenous (IV) infusion of L-tryptophan (200 mg/kg/h) or an equal volume (2 ml/h) of saline. Ninety minutes into the infusion, cocaine (20 mg/kg) was injected intra-peritoneally. Cocaine increased nucleus accumbens microdialysate dopamine levels (500% at 30 min). This was associated with marked hyperactivity. Tryptophan infusion elevated plasma tryptophan (8-fold), and blunted the cocaine-induced increase in nucleus accumbens microdialysate dopamine levels by approximately 60%. Furthermore, tryptophan attenuated the cocaine-induced locomotor activity. These neurochemical and behavioral effects of tryptophan were associated with a marked increase in brain tissue serotonin content. The results of these studies demonstrate the feasibility of acute dietary manipulation of neurochemical and behavioral responses to cocaine. The duration, adaptation and tolerance to these effects remain to be elucidated.

Animals↗
PubMed2001

Epitopes in the interacting regions of beta-dystroglycan (PPxY motif) and dystrophin (WW domain).

The dystroglycan gene produces two products from a single mRNA, the extracellular alpha-dystroglycan and the transmembrane beta-dystroglycan. The Duchenne muscular dystrophy protein, dystrophin, associates with the muscle membrane via beta-dystroglycan, the WW domain of dystrophin interacting with a PPxY motif in beta-dystroglycan. A panel of four monoclonal antibodies (MANDAG1-4) was produced using the last 16 amino acids of beta-dystroglycan as immunogen. The mAbs recognized a 43 kDa band on Western blots of all cells and tissues tested and stained the sarcolemma in immunohistochemistry of skeletal muscle over a wide range of animal species. A monoclonal antibody (mAb) against the WW domain of dystrophin, MANHINGE4A, produced using a 16-mer synthetic peptide, recognized dystrophin on Western blots and also stained the sarcolemma. We have identified the precise sequences recognized by the mAbs using a phage-displayed random 15-mer peptide library. A 7-amino-acid consensus sequence SPPPYVP involved in binding all four beta-dystroglycan mAbs was identified by sequencing 17 different peptides selected from the library. PPY were the most important residues for three mAbs, but PxxVP were essential residues for a fourth mAb, MANDAG2. By sequencing five different random peptides from the library, the epitope on dystrophin recognized by mAb MANHINGE4A was identified as PWxRA in the first beta-strand of the WW domain, with the W and R residues invariably present. A recent three-dimensional structure confirms that the two epitopes are adjacent in the dystrophin-dystroglycan complex, highlighting the question of how the two interacting motifs can also be accessible to antibodies during immunolocalization in situ.

Amino Acid Motifs↗
PubMed2001

The alphaVbeta6 integrin regulates its own expression with cell crowding: implications for tumour progression.

Expression of the growth-promoting integrin alphavbeta6 in colon cancer cells induces gelatinase B secretion and activation, the inhibition of which abolishes alphavbeta6-mediated tumour cell growth within a collagen matrix. Herein, we show that high cell density selectively enhances alphavbeta6 expression in a protein kinase C (PKC)-dependent manner in preference to other beta integrin subunits, resulting in a marked increase in gelatinase B secretion as cells reach confluence. Moreover, PKC activity increases with cell confluence, and the rise in PKC activity is much greater for alphavbeta6-expressing cells than for colon cancer cells which lack alphavbeta6. We propose a self-perpetuating system of colon cancer progression in which the integrin alphavbeta6 provides a means of sustaining tumour cell proliferation. In this model, alphavbeta6 regulates its own expression via a PKC-mediated signalling pathway as tumour cells become crowded and quiescent. The alphavbeta6-mediated induction of gelatinase B secretion facilitates peri-cellular matrix degradation, which helps overcome crowding and restores cell proliferation.

Antigens, Neoplasm↗
PubMed2001

Vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 serum level in patients with chest pain and normal coronary arteries (syndrome X).

BACKGROUND: Plasma levels of soluble vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) mediators of leukocyte adhesion to vascular endothelium may implicate in the pathogenesis of the syndrome of chest pain with normal coronary arteries. HYPOTHESIS: We attempted to determine whether markers of endothelial activation are raised in patients with chest pain and normal coronary arteries. METHODS: We measured plasma VCAM-1, ICAM-1 (ng/ ml) in 36 patients (34 men, 2 women, aged 62 +/- 9 years) with stable angina, coronary artery disease (CAD), and a positive response to exercise test; in 21 patients (6 men, 15 women, aged 56 +/- 9 years) with chest pain and normal coronary arteriograms (syndrome X); and in 11 healthy control subjects (8 men, 3 women, aged 49 +/- 14 years). RESULTS: Plasma ICAM-1 levels were significantly higher both in patients with CAD (mean +/- standard error of the mean) (328 +/- 26, p < 0.05), and in syndrome X (362 +/- 22, p < 0.01) than in controls (225 +/- 29). VCAM-1 levels were also higher in syndrome X (656 +/- 42 ng/ml) and in patients with CAD (626 +/- 42 ng/ml) than in controls (551 +/- 60, p = 0.09). CONCLUSIONS: ICAM-1 and VCAM-1 levels are increased both in patients with CAD and with syndrome X compared with control individuals. These findings may suggest the presence of chronic inflammation with involvement of the endothelium in patients with anginal chest pain and normal coronary angiograms.

Adult↗