Biomedical subjects

M Horiguchi

Publications and source records attributed to M Horiguchi.

At least 37 records · Page 2Linked to original sources

PubMed1999

Mutagenicity of 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) in the new gpt delta transgenic mouse.

Gender differences and organ specificity of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mutagenesis were examined with the new gptdelta transgenic mouse (T. Nohmi, M. Katoh, H. Suzuki, M. Matsui, M. Yamada, M. Watanabe, M. Suzuki, N. Horiya, O. Ueda, T. Shibuya, H. Ikeda, T. Sofuni, A new transgenic mouse mutagenesis test system using Spi-and 6-thioguanine selections (Environ. Mol. Mutagen. 28 (1996) 465-470). In this mouse model, two distinct selections are employed to efficiently detect different types of mutations, i.e 6-thioguanine (6-TG) selection for point mutations and Spi-selection for deletions, respectively. In both selections, the highest mutant frequencies were observed in colon, followed by in spleen and liver. No increases in mutations were observed in testis, brain and bone marrow in PhIP-treated male mice. No significant differences in 6-TG and Spi- mutant frequencies were observed in colon and liver between male and female treated mice. The correlation between PhIP-induced mutagenesis and carcinogenesis in colon is discussed.

Animals↗

PubMed1999

Morphogenesis of the primary arterial trunks of the forelimb in the rat embryos: the trunks originate from the lateral surface of the dorsal aorta independently of the intersegmental arteries.

It has been believed that the primary arterial trunk of the mammalian forelimb is derived from the 7th intersegmental artery. Here we examined the early morphogenesis of the arteries and nerves in the forelimb region by adopting a method that combined intravascular dye-injection with nerve staining to whole mounted rat embryos. The study was carried out on greater numbers of specimens at smaller intervals of embryonic stages and from earlier stages than those in previous reports. We report that: (1) The multiple primary arterial trunks in the forelimb region (primary subclavians) originate directly from the lateral surface of the dorsal aorta independently of the intersegmental arteries, previous to the formation of limb buds. (2) The tips of the 8th (and the 9th) primary subclavians that originate from the aorta near the origin of the 8th (or the 9th) intersegmental artery bend cranially and/or caudally. With the formation of limb bud, they extend to form the longitudinal trunks in the presumptive axillary region. The primary arteries in the free arm region branch off from this longitudinal trunk, and one of them develops into the axial artery. (3) The origins of the primary subclavians shift their positions on the surface of the dorsal aorta and approach the origins of the neighboring intersegmental arteries to join them, and then replace the latter. Consequently, the primary subclavians appear to be "the lateral branches of the in tersegmental arteries." (4) The 8th primary subclavian is dominant at first, but is replaced by the 7th primary subclavian, which develops into the definitive subclavian artery. (5) With the brachial nerve plexus formation, the axillary arterial plexus derived from the longitudinal trunk develops to form two stems of the axillary artery.

Animals↗

PubMed1999

Abnormal focal macular electroretinograms in eyes with idiopathic epimacular membrane.

PURPOSE: To study the functional state of the retina beneath an epimacular membrane by means of focal macular electroretinography. METHODS: Focal macular electroretinograms of 30 consecutive patients (age 25 to 75 years) with unilateral idiopathic epimacular membrane were recorded prospectively. The amplitudes and implicit times of the a and b waves and the oscillatory potentials (O1, O2, O3) recorded from the eye with idiopathic epimacular membrane were compared with those of the normal fellow eye. RESULTS: There was a statistically significant reduction in the amplitude of the a wave (P < .001), the b wave (P < .001), and the oscillatory potentials (O1 + O2 + O3; P < .001) of the affected eyes. The reduction of the b-wave amplitude was significantly greater than that of the a wave, resulting in a lower b/a wave ratio (P = .003) in the affected eyes. The reduction in the amplitude of the oscillatory potentials was significantly greater than that of the other two components (P < .001). The implicit times were significantly prolonged for the a wave (P < .001), the b wave (P = .004), and 03 (P < .001). There was a significant correlation between relative b-wave amplitude (affected/normal fellow eye) and the visual acuity (r = -0.50, P = .007). These findings were similar to those we reported for eyes with aphakic cystoid macular edema. CONCLUSIONS: The focal macular electroretinograms in eyes with epimacular membrane disclosed abnormalities that were similar to those of eyes with cystoid macular edema. This suggests that the epimacular membrane probably induced damage to the neurons in the inner retinal layers. Dysfunction of these neurons is one possible cause of visual impairment in this disease.

Adult↗

PubMed1999

The relationship between Ca2+-ATPase and freely exchangeable Ca2+ in the dense tubules: a study in platelets from women.

The main aims of this work were to examine in women: the relationship between the freely exchangeable Ca2+ (FECa2+) in the dense tubules and the activity of the sarco(endo)plasmic reticulum (SER) Ca2+-ATPase (SERCA) in platelets, and the relationship of these parameters with blood pressure and serum lipoproteins. Platelets from 14 white and 13 black women in good health were studied. The FECa2+ was measured as the ionomycin-evoked Ca2+ release (in the presence of thapsigargin) in Ca2+-free medium. SERCA activity was measured as the thapsigargin sensitive, Ca2+ dependent and ouabain resistant, ATP hydrolyses in platelet membranes. Relative expressions of SERCA 2 and 3 isoforms and Ras-related protein (Rap) 1 in platelet membranes were determined by Western immunoblots. Highly significant correlations were observed for FECa2+ in the dense tubules with: 1) the maximal reaction velocity (Vmax) of the SERCA (r = 0.592, P = .0014), and 2) Rapl (r = 0.551, P = .0035). In addition, negative correlations were observed between FECa2+ in the dense tubules and age. No correlations were observed for these variables with blood pressure or serum lipoproteins. We conclude the FECa2+ and the Vmax of the SERCA are reliable indicators of Ca2+ load in platelets from women. However, in women, unlike previous observations in men, these platelet parameters are not correlated with blood pressure and serum lipoproteins.

Adult↗

PubMed1999

Immunocytochemical features of lens after cataract tissue--signalling molecules (growth factors, cytokines, other signalling molecules), cytoskeleton proteins, cellular and extracellular matrix proteins.

UNLABELLED: We examined the immunocytochemical features of after cataract tissue and cataractous lens epithelium prior to cataract surgery and at the time of surgery. METHODS: This study included 23 cases. Antibodies against the following antigens were used: epidermal growth factor (EGF), EGF receptor (EGF-R), fibroblast growth factor (FGF), FGF receptor (FGF-R), transforming growth factor (TGF)-beta, TGF-beta receptor II (TGF-beta -RII), insulin-like growth factor (IGF)II, platelet derived growth factor (PDGF)-AB, interleukin (IL)-6, IL-1 receptor II, tumor necrosis factor (TNF)-alpha, tissue plasminogen activator (TPA), prostaglandin (PG) E2, plasminogen activator inhibitor (PAI)-1, alpha smooth muscle actin (alpha-SMA), keratin, vimentin, myosin, fibronectin, laminin, types I, II, III, IV, V and VI collagen (Col), and lens epithelial cells (LECs). RESULTS: The following substances were present in posterior and anterior capsular fibrosis of after cataract: EGF, EGF-R, FGF, FGF-R, TGF-beta, TGF-beta-RII, IGF-II, PDGF-AB, IL-6, IL-1RII, TNF-alpha, PGE2, PAI-1, alpha-SMA, keratin, fibronectin, laminin, Type I col, Type II to VI col and LECs. Elschnig's pearls of after cataract expressed FGF-R, TNF-alpha, laminin and LECs. Soemmering's ring of after cataract tissue expressed EGF, FGF, FGF-R, IL-1RII, TPA, PAl-1, keratin and LECs. The following substances were present in cataractous lens epithelium prior to cataract surgery: EGF, EGF-R, FGF, FGF-R, TGF-beta-RII, IL-1-RII, TNF-alpha, PAI-1, keratin, laminin and LECs. The following substances were present in the lens epithelium of anterior capsules collected at the time of cataract surgery: EGF, EGF-R, FGF, FGF-R, TGF-beta, TGF-beta-RII, IGF-II, IL-6, IL-1-RII, TNF-alpha, PGE2, keratin, fibronectin, laminin, Type IV Col and LECs. CONCLUSIONS: These results prove that many kinds of signalling molecules and proteins exist in the process of after cataract formation.

Aged↗

PubMed1999

The consistent presence of the human accessory deep peroneal nerve.

Twenty-four human legs were dissected macroscopically to study the morphological details of the accessory deep peroneal nerve. This nerve arose from the superficial peroneal nerve and descended in the lateral compartment of the leg, deep to peroneus longus along the posterior border of peroneus brevis. Approaching the ankle joint, this nerve passed through the peroneal tunnels to wind around the lateral malleolus; it then crossed beneath the peroneus brevis tendon anteriorly to reach the dorsum of the foot. The accessory deep peroneal nerve was found in every case examined and constantly gave off muscular branches to peroneus brevis and sensory branches to the ankle region. In addition, this nerve occasionally had muscular branches to peroneus longus and extensor digitorum brevis, and sensory branches to the fibula and the foot. The anomalous muscles around the lateral malleolus were also innervated by this nerve. Neither cutaneous branches nor communicating branches with other nerves were found. The present study reveals that the accessory deep peroneal nerve is consistently present and possesses a proper motor and sensory distribution in the lateral region of the leg and ankle. It is not an anomalous nerve as has previously been suggested.

Ankle Joint↗

PubMed1999

Effect of rotational alignment on patellar tracking in total knee arthroplasty.

Forty-four consecutive patients (65 knees) who underwent identical condylar type total knee arthroplasty were evaluated retrospectively. In 22 of the patients (32 knees), the femoral component was set parallel to the posterior condylar axis (neutrally aligned group). In the remaining 22 patients (33 knees), it was set in an external rotation position of 3 degrees to 5 degrees relative to the axis (externally aligned group). Of the total knee arthroplasties in the neutrally aligned group, 34% required lateral release, compared with only 6% in the externally aligned group; patellar tracking in the externally aligned group was significantly better than that in the neutrally aligned group. Postoperative measurements performed using computed tomography scans showed that the mean angle between the prosthetic posterior condylar axis and the transepicondylar axis was 7.9 degrees in the neutrally aligned group and 3.2 degrees in the externally aligned group. The external rotation setting of the femoral component diminished the need for lateral retinacular release and may decrease the rate of patellofemoral complications that occur after total knee arthroplasty.

Adult↗

PubMed1999

The human suprascapular nerve belongs to both anterior and posterior divisions of the brachial plexus.

For the sake of clarifying which division of the brachial plexus, anterior or posterior, does the human suprascapular nerve belong to, the suprascapular nerve and cervical nerves concerned were teased into bundles of fibers by the fiber analysis method in six adult human arms of cadavers. The suprascapular nerve received fibers from C4, C5 and C6 in two cases which have a communicating branch between C4 and C5, from C6 and C6 in three cases and only from C5 in one case. In contrast with the posterior root fibers, the anterior root fibers of C5 and C6 could easily be divided into anterior and posterior groups of bundles which entered the anterior and the posterior divisions of the brachial plexus and were called anterior motor and posterior motor elements respectively. The suprascapular nerve received fibers from the anterior and the posterior motor elements of C5 in all cases. In addition to the C5, the nerve received fibers from both elements of C6 in three cases or from the anterior element of C6 in two cases. From this result the suprascapular nerve is judged to be a nerve which belongs to both anterior and posterior divisions of the brachial plexus.

Adult↗

PubMed1999

Immunochemical characterization of ovomucoid from Japanese quail egg white using monoclonal antibodies.

The ovomucoid of Japanese quail egg white is known as a proteinase inhibitor or protein component responsible for egg allergy. In order to characterize the antigenic properties of ovomucoid in relation to its molecular structure, we have prepared two monoclonal antibodies, E9 (IgG1) and E11 (IgG1), recognizing distinct epitopes from each other. These monoclonal antibodies bound to the SDS/mercaptoethanol-treated ovomucoid, but not to the reductively carboxymethylated and pyridylethylated ovomucoid. By immunoblotting analysis of the peptic digests of ovomucoid, it was shown that E9 bound to the fragment consisting of two domains, I and II, of the ovomucoid, and that E11 reacted with the fragment containing domain III. These results indicate that the antigenic activity depends on the conformational structure of domains tightly folded by disulfide linkages. Ovomucoids from hen and duck were also recognized by both the antibodies, although having less affinity compared to the one from Japanese quail. These antibodies proved to be effective in establishing an enzyme-linked immunosorbent assay system for quantitative analysis of quail ovomucoid.

Amino Acid Sequence↗

PubMed1999

Amplitude increase of the multifocal electroretinogram during light adaptation.

PURPOSE: To determine using the multifocal ERG technique whether there are any regional differences in the increase in the amplitude of cone electroretinograms (ERGs) during light adaptation. METHODS: Multifocal ERGs were recorded with the Visual Evoked Response Imaging System from five normal subjects. Thirty-seven hexagonal stimulus elements and a recording time of 60 seconds were used. After 20 minutes of dark adaptation, multifocal ERGs were repeatedly recorded every 2 minutes over a period of 16 minutes. The amplitudes of the multifocal ERGs at different eccentricities were compared during the 16 minutes of light adaptation. RESULTS: During the 16 minutes of light adaptation, the summed responses of the multifocal ERGs increased in amplitude an average of 36% and 47% for the negative and positive components, respectively. The magnitude of increase was minimal in the central retina at 22% and was significantly larger in the peripheral retina at 58%. The implicit time was slightly increased (<4%) with light adaptation, but there were no regional differences. CONCLUSIONS: The results demonstrated that there are topographic variations in the amplitude increase of cone ERGs during light adaptation. This topographic variation indicates that the mechanism for the increase must be based on known regional differences in the retina.

Adaptation, Ocular↗

PubMed1999

Blue-on-yellow perimetry in the complete type of congenital stationary night blindness.

PURPOSE: To resolve the discrepancy between nonrecordable full-field short wavelength cone electroretinograms (S-cone ERGs) and the presence of normal color vision in patients with the complete type of congenital stationary night blindness (CSNB1). METHODS: Conventional white-on-white (W-W) perimetry, blue-on-yellow (B-Y) perimetry, and the Farnsworth-Munsell 100-hue test were performed in five patients with CSNB1. Diagnosis of CSNB1 was made by clinical and electrophysiological examinations. Twelve normal, age-matched control subjects and an additional 7 normal, highly myopic subjects were tested. RESULTS: Color vision was normal in all the CSNB1 patients by the Farnsworth-Munsell 100-hue test. B-Y perimetry demonstrated that blue cone sensitivity in CSNB1 was normal in the fixation area, but the mean sensitivities of the entire 60 degrees field, the central 0 degrees-to-15 degrees, and 15 degrees-to-30 degrees ring were significantly decreased compared with the normal and myopic subjects. The sensitivity difference between 15 degrees-to-30 degrees and 0 degrees-to-15 degrees in B-Y perimetry increased significantly in CSNB1 compared with both normal and myopic control subjects. CONCLUSIONS: Our perimetric results demonstrated that the S-cone function in CSNB1 is preserved only in the fovea and becomes abnormal toward the peripheral retina. This accounts for the normal color vision that tests mainly foveal function and the nonrecordable S-cone ERGs that arise mainly from peripheral retina.

Adolescent↗

PubMed1999

UVB-induced gpt mutations in the skin of gpt delta transgenic mice.

Ultraviolet light B (UVB)-induced mutagenesis was studied in gpt delta transgenic mice, which contain the lambdaEG10 shuttle vector as a transgene. The mice were exposed to UVB at single doses of 0.3, 0.5, 1.0, 1.5, and 2.0 kJ/m(2). At 4 weeks after irradiation, the mutant frequencies (MF) of the gpt gene were determined in the epidermis and the dermis, and the gpt mutations in the epidermis were identified by DNA sequencing. The epidermis exhibited a higher sensitivity to UVB than the dermis at doses of 0.3 and 0.5 kJ/m(2) UVB: the MF of the epidermis were more than nine times higher than those of the nonirradiated mice, whereas the MF of the dermis were only two to three times higher than the nonirradiated level at the doses used. The UVB-induced mutation spectrum in the epidermis was dominated by G:C to A:T transitions at dipyrimidine sites, such as 5'-TC-3', 5'-CC-3', and 5'-T/C-CG-3'. Tandem transitions such as CC to TT were also observed. Interestingly, a remarkable bias towards the template strand of the gpt gene was observed in the single transitions at 5'-TC-3' and 5'-CC-3' sites, but not at 5'-T/C-CG-3' site. In contrast, G:C to A:T transitions at CpG sites and deletions were observed in nonirradiated mice. Hot spots of transitions were observed at different sites in UVB-irradiated and nonirradiated mice. These results indicate that gpt delta transgenic mouse is a suitable model for studying in vivo UVB-induced mutations at the molecular level.

Animals↗

PubMed1998

Staining of the lens capsule for circular continuous capsulorrhexis in eyes with white cataract.

We have developed a technique of staining the anterior capsule with a solution of indocyanine green that facilitates performance of the circular continuous capsulorrhexis in eyes with a mature cataract. We compared the results of phacoemulsification and intraocular lens implantation in 10 eyes with the capsule stained with results of 10 eyes having the same procedure with standard circular continuous capsulorrhexis. The results of specular microscopy and laser flare-cell photometry showed no statistically significant differences between the 2 groups. Although the safety of intraocular indocyanine green dye has not yet been definitively established, the findings of this pilot study suggest that it is safe and useful in visualizing the anterior capsule of a mature cataract during cataract surgery.

Aged↗

PubMed1998

Electroretinographic alterations during vitrectomy in human eyes.

BACKGROUND: We previously reported a new system of electroretinographic monitoring of the retinal function during vitrectomy in human eyes, and found that lowering the intravitreal temperature by applying an infusion solution kept at room temperature (used routinely for vitrectomy throughout the world) can alter the electroretinogram (ERG). This time we attempted to study the effect upon the ERG of replacing the intraocular medium and acutely elevating the intraocular pressure during vitrectomy. METHODS: Using a special contact lens with a built-in light-emitting diode light source, 30-Hz flicker ERG was quickly recorded under aseptic conditions. RESULTS: Acute, reversible reduction in amplitude was observed upon replacing the intraocular medium with air or silicon oil and during periods of acutely elevated intraocular pressure. Infusions of gentamicin or miconazole did not affect the ERG when intravitreal temperature and intraocular pressure were constant. CONCLUSION: The ERG monitor can reveal changes of the retinal function during vitrectomy, particularly when the infusion temperature, intraocular medium and intraocular pressure are kept constant.

Antifungal Agents↗

PubMed1998

Focal macular electroretinograms before and after successful macular hole surgery.

PURPOSE: To report changes in focal macular electroretinograms before and after successful macular hole surgery and to discuss whether preoperative retinal function can predict postoperative visual acuity. METHODS: In this prospective study, 28 consecutive eyes of 28 patients underwent vitrectomy for stage 2 or 3 full-thickness idiopathic macular hole. Focal macular electroretinograms using a 4-degree stimulus spot were obtained in 24 eyes of 28 patients, and those using a 5-degree stimulus spot were obtained in 24 eyes of 28 patients, to evaluate preoperative and postoperative amplitude and implicit time of the b-wave. Visual acuity was measured preoperatively and postoperatively, and results were translated into logMAR (minimum angle of resolution) values. RESULTS: After successful macular hole closure, the b-wave amplitude increased in 23 of 24 eyes measured with the 4-degree stimulus spot and in 19 of 24 eyes measured with the 5-degree stimulus spot. Postoperative b-wave amplitude recorded with either stimulus spot correlated with postoperative corrected visual acuity. The b-wave implicit time decreased in 15 of 20 eyes measured with the 4-degree spot and in 13 of 23 eyes measured with the 5-degree spot. Preoperative b-wave implicit time measured with the 5-degree stimulus spot correlated significantly (P = .001) with postoperative corrected visual acuity. CONCLUSIONS: Qualitative change (implicit time) is more important than quantitative change (amplitude) in electroretinograms for predicting postoperative corrected visual acuity. The function of the retinal tissue surrounding the hole may affect visual outcome.

Adult↗

PubMed1998

Liquefied aftercataract: a complication of continuous curvilinear capsulorhexis and intraocular lens implantation in the lens capsule.

PURPOSE: To describe a new type of aftercataract that contains a liquefied, milky white substance between the lens optic and the posterior lens capsule. METHOD: We reviewed the medical records of 41 patients identified as having this type of aftercataract. RESULTS: All 41 eyes (41 patients) underwent uneventful phacoemulsification after continuous curvilinear capsulorhexis and implantation of a posterior chamber intraocular lens made from polymethylmethacrylate. Two months to 6 years after surgery (average+/-SD, 3.8+/-1.7 years), fibrosis was noted evenly along the entire circumference and between the anterior surface of the intraocular lens optic and the edge of the capsular opening created by continuous curvilinear capsulorhexis. This led to formation of a closed chamber between the intraocular lens and the posterior lens capsule, which then accumulated a liquefied, milky white substance. Twenty-three of the 41 eyes showed liquefied aftercataract in conjunction with other types of aftercataract: in 12 eyes with fibrosis, in 11 eyes with Elschnig pearls, and in one eye with a Soemmering ring. None of the eyes had any signs of inflammation; six of the 41 eyes had reduced visual acuity caused exclusively by the liquefied aftercataract. Before cataract surgery, 14 eyes were diagnosed with diabetic retinopathy, four with glaucoma, and two with uveitis. CONCLUSION: We report a new type of aftercataract characterized by a liquefied, milky white substance that accumulates between the lens optic and the posterior lens capsule when the anterior capsular opening, originally created by continuous curvilinear capsulorhexis, becomes occluded with the lens optic.

Adult↗

PubMed1998

Extrafoveal photostress recovery test in glaucoma and idiopathic central serous chorioretinopathy.

BACKGROUND/AIMS: A photostress recovery test was designed to differentiate macular diseases from optic nerve disorders, but recently an abnormal recovery time was reported in glaucoma. The purpose of this study was to search for the difference in abnormality of the photostress recovery test between glaucoma and idiopathic central serous chorioretinopathy (ICSC). METHODS: This study involved 21 normal subjects, 14 patients, with ICSC and 10 patients with primary open angle glaucoma (POAG). A scanning laser ophthalmoscope (SLO) was used with microperimetry for bleaching the test point and measuring the recovery of sensitivity. Photostress recovery time (SLO-PSRT) could be measured at extrafoveal points outside and inside the affected area. The initial sensitivity change and the time constant of recovery after bleaching were calculated by fitting an exponential equation to the data. RESULTS: In normal subjects, neither the initial sensitivity change nor the time constant were correlated with the location of the test point. In 14 patients with ICSC, the initial sensitivity change in the detached area was significantly smaller than that in the unaffected area which was not significantly different from that in the age matched normal subjects. The time constant in the detached area was significantly longer than that in the unaffected area, which was not significantly different from that in the normal subjects. In 10 patients with POAG, the initial sensitivity change inside and outside the scotoma was not significantly different from that of age matched normal subjects. The time constant inside the scotoma was significantly longer than that outside the scotoma, which was not significantly different from that of the age matched normal subjects. CONCLUSION: Both ICSC and POAG showed a prolonged time constant of recovery, but the initial sensitivity change was reduced only in ICSC. The difference in our results between ICSC and POAG may be caused by the difference of the retinal pathology. Further, the SLO-PSRT is very useful when the lesion is located outside the fovea.

Adult↗

PubMed1998

Ca2+ in the dense tubules: a model of platelet Ca2+ load.

In this work, we explored the relationship between the freely exchangeable Ca2+ (FECa2+) in the dense tubules (DT) and the sarco(endo)plasmic reticulum (SER) Ca2+-ATPase (SERCA) in circulating human platelets and examined the relationship between blood pressure (BP) and these platelet parameters. Studying platelets from 32 healthy men, we showed that the maximal reaction velocity (Vmax) of the SERCA significantly correlated with FECa2+ in the DT and with the protein expressions of SERCA 2 and 3. BP positively correlated with both the Vmax of the SERCA (r=.462, P=.010) and the FECa2+ sequestered in the DT (r=.492, P=.005). The relationships between these platelet Ca2+ parameters and BP were in part confounded by increased levels of serum triglycerides and diminished HDL cholesterol with a higher BP. No correlation was observed between the resting cytosolic Ca2+ and BP. Collectively, these findings indicate that (1) an increase in the cellular Ca2+ load in platelets is expressed by a higher activity of the SERCA and an increase in the expressions of SERCA 2 and 3 proteins, coupled with an increase in the FECa2+ in the DT, and (2) a higher BP is associated with an increase in platelet Ca2+ load in human beings, expressed by a rise in the FECa2+ in the DT and the upregulation of SERCA activity.

Adult↗