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T Nagamine

Publications and source records attributed to T Nagamine.

At least 109 records · Page 6Linked to original sources
PubMed1999

A tourist element in the 5'-flanking region of the catalase gene CatA reveals evolutionary relationships among Oryza species with various genome types.

Tourist-OsaCatA, a transposable element, was found in the 5'-flanking region of the rice gene CatA. The characteristics of this element are similar to those of the other Tourist elements so far found in Oryza sativa. PCR and sequence analyses of 37 accessions of 18 species revealed that all the Oryza species examined, except for one accession, have either a full-length or a partial Tourist element at this locus. Unlike the Tourist elements previously reported, this Tourist element is found in all four Oryza species complexes in the Oryzeae tribe. All AA genome Oryza species, except O. longistaminata, contain the full-length Tourist element. O. longistaminata and the species of the O. officinalis, O. meyeriana and O. ridleyi complexes contain the partial element. A phylogenetic tree of Oryza species based on the nucleotide sequences of these Tourist elements was constructed. The O. longistaminata accessions were placed near the neighboring cluster of the officinalis complex. We propose that the ancestor of O. longistaminata and that of other species with the AA genome diverged, and the ancestor(s) of the O. officinalis, O. ridleyi and O. meyeriana complexes then diverged from the ancestor of O. longistaminata in the course of the evolution of the Oryza species. The Tourist elements associated with CatA and its orthologs thus provide useful tools for examining evolutionary relationships among Oryza species.

Base Sequence↗
PubMed1999

Nausea and vomiting induced by arterial chemo-embolization in patients with hepatocellular carcinoma and the antiemetic effect of ondansetron hydrochloride.

To determine the incidence of nausea and vomiting and the antiemetic effect of ondansetron hydrochloride (OND) in patients with hepatocellular carcinoma treated with arterial chemo-embolization, we studied 59 patients with hepatocellular carcinoma who were treated with transcatheter arterial embolization (TAE) or lipiodolized transcatheter arterial infusion (L-TAI). We investigated the incidence of nausea and vomiting and the amount of food intake when TAE or L-TAI was performed. All patients who experienced nausea and vomiting received OND administered prophylactically at the time of the next TAE or L-TAI to evaluate the antiemetic effect of the drug. Cumulative rates of nausea and vomiting during the week following arterial chemo-embolization were 44.8% and 27.6%, respectively. There was a tendency for the incidence to be higher in patients treated with the anticancer agent zinostatin stimalamer (SMANCS) than in those treated with epirubicin hydrochloride (EPI). Regarding food intake, 53.1% of the patients stated that they ate "half or more than half" of the food provided on the day of arterial chemo-embolization. The rate improved as time went on. In 5 patients who experienced nausea and vomiting at the time of arterial chemo-embolization, nausea and vomiting were inhibited satisfactorily by OND. When arterial chemo-embolization was performed, antiemetic treatment for approximately 3 days was necessary to improve patients' quality of life (QOL) to an acceptable level, and OND was found to be effective for the purpose in our 5 patients who had experienced nausea and/or vomiting at the previous treatment.

Adult↗
PubMed1999

Screening of antioxidant action of various molds and protection of Monascus anka against experimentally induced liver injuries of rats.

Antioxidant action of various molds, which are traditionally used for the production of foods or alcoholic beverages in Japan, was studied in vitro and in vivo. Antioxidant action was evaluated by scavenging stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH) and lipid peroxidation of rat liver microsomes. Among 40 molds, 16 species showed the DPPH scavenging action, and the molds that can scavenge the DPPH radical inhibited lipid peroxidation. The mold with the strongest action, Monascus anka, was chosen for the investigation of a protective action against liver injury of rats. When galactosamine (GalN, 400 mg/kg) or GalN plus lipopolysaccharide (LPS, 0.5 microg/kg) was given intraperitoneally to rats (Sprague-Dawley), aspartate aminotransferase (AST) and glutathione (GSH) S-transferase (GST) activities in serum were significantly increased. However, such hepatotoxicities seen in the increase in serum enzyme levels were depressed when the extract prepared from M. anka was given 1 and 15 h before the toxic insultant. Liver microsomal GST activity, which is known to be activated by oxidative stress, was increased by GalN or GaIN plus LPS treatment and the increase was also inhibited by pretreatment with the extract. Pathomorphological changes in the liver caused by GalN treatment also were prevented by the mold extract. These results indicate that the extract of M. anka has radical scavenging action and ameliorates chemically induced hepatotoxicity.

Animals↗
PubMed1999

Movement-related cortical potentials associated with voluntary relaxation of foot muscles.

OBJECTIVE: In our previous study of movement-related cortical potential (MRCP) in association with the voluntary relaxation of the hand muscle, Bereitschaftspotential (BP) was maximal at the vertex and symmetrically distributed, and Negative Slope (NS') was maximal over the contralateral central region. In order to clarify the generator sources of MRCP with voluntary muscle relaxation, we recorded MRCP in association with voluntary relaxation of the foot. METHODS: MRCP in association with plantar flexion of the foot caused by voluntary relaxation of the tibialis anterior muscle was recorded in 10 normal subjects. RESULTS: The BP started at about 1.7 s before the onset of the muscle relaxation, followed by NS' starting at about 650 ms before it. Both were maximal at the vertex and symmetrically distributed. There was no additional EEG activity in the lateral frontal areas, which are presumably located over the primary negative motor areas (PNMA). CONCLUSIONS: It is concluded that the voluntary muscle relaxation, similarly to the voluntary muscle contraction, involves the cortical preparatory activity at least in the primary motor area (M1) and probably the supplementary motor areas (SMAs). There is no evidence to suggest that the PNMA is also active prior to the voluntary muscle relaxation.

Adult↗
PubMed1999

Construction of Prevotella ruminicola-Escherichia coli shuttle vector pRAM45 and transformation of P. ruminicola strains by electroporation.

A new plasmid shuttle vector, pRAM45, was constructed from the Escherichia coli plasmid pACYC184 and the cryptic plasmid pRAM4, which was originally isolated by us from Prevotella ruminicola T31 (Ogata et al., Plasmid, 35, 91-97, 1996). The vector was electrotransformed into different P. ruminicola strains. Polymerase chain reaction and Southern hybridization experiments confirmed its integrity in P. ruminicola transformants.

Journal Article↗
PubMed1999

Evaluation of twice-daily administration of interferon-beta for chronic hepatitis C.

To improve the efficacy of interferon (IFN) in the treatment of chronic hepatitis C, administration of IFN-beta twice per day was evaluated. Thirty-eight patients with chronic hepatitis C (26 males and 12 females, aged 25-67 years) were included. Patients were treated with a new protocol that included twice-daily treatment with IFN-beta. Three million units (MU) of IFN-beta was administered twice daily every day for 4 weeks followed by 10 MU of IFN-alpha2b, every day for 2 weeks and then three times a week for 18 weeks (total IFN-beta, 148 MU; IFN-alpha2b, 680 MU). Complete responders (CR) were defined by alanine aminotransferase levels that normalized within 6 months after completion of IFN therapy and remained normal for more than 6 months, and by serum hepatitis C virus (HCV) RNA levels that became negative as determined using the Amplicor assay. Twenty-one of 38 (55.3%) patients were CR. Nine of 21 (42.9%) patients with HCV serotype 1 were responders compared with nine of 12 (75.0%) patients with HCV serotype 2. In patients with an HCV titre greater than 1 million equivalents ml-1 (1 MEq ml-1), nine of 24 (37.5%) responded, and in patients with HCV titres less than 1 MEq ml-1, 12 of 14 (85.7%) responded. In patients with HCV serotype 1 and greater than 1 MEq ml-1 HCV RNA, four of 15 (26.7%) responded to IFN. Two-thirds (66.7%) of the patients who became negative for HCV RNA after 2 weeks of therapy responded, while 72.7% of those with positive HCV RNA after 2 weeks of therapy were non-responders. Proteinuria was frequently observed as an adverse effect of twice-daily administration of IFN-beta. The combination of twice-daily administration of IFN-beta for 4 weeks followed by IFN-alpha showed a high response rate in patients with chronic hepatitis C, but in patients with both serotype 1 and a high titre of HCV RNA, response rates were still low. Thus, the HCV RNA titre 2 weeks after starting therapy with IFN was useful for predicting the eventual response to IFN.

Adult↗
PubMed1999

The role of the hippocampus in auditory processing studied by event-related electric potentials and magnetic fields in epilepsy patients before and after temporal lobectomy.

To clarify the relationship between the hippocampus and the event-related responses in auditory information processing, we recorded event-related potentials (ERPs) and event-related magnetic fields (ERFs) associated with the auditory oddball paradigm in 12 patients with temporal lobe epilepsy before and after surgical treatment, and in eight age-matched healthy volunteers. Lesions in the patients were hippocampal sclerosis (8), cyst (2), cavernoma (1) and calcified arteriovenous malformation (1), all in the unilateral temporal lobe. Standard temporal lobectomy (8), selective amygdalohippocampectomy (2), selective hippocampectomy (1) and inferior lateral temporal resection (1) were carried out. ERPs were recorded in nine patients before surgery, in all 12 patients after surgery, and in all normal subjects. P300 was maximal at Pz in the patients both before and after surgery, and in normal subjects. The peak latency and amplitude of P300 measured at Pz in the patients either before or after surgery did not differ significantly from those in normal subjects. After surgery, only the amplitude of P300 over the anterior and mid-temporal area on the resected side was attenuated, while it was symmetric before surgery regardless of the side of epileptogenic focus. ERFs were recorded in three patients before surgery and in six normal subjects by using a whole-head neuromagnetometer. ERFs in response to the target stimuli at a latency of approximately 400 ms were recognized at the anterior, middle and posterior lateral channels on each hemisphere (M400). The latency and dipole moments for M400 did not differ significantly between the patients before surgery and the normal subjects. As a result of analysis using the time-varying multidipole model, three dipoles for M400 were estimated in two patients in whom ERFs were available before surgery for the analysis, and in normal subjects: mesial temporal area, superior temporal area and inferior parietal area on each hemisphere. After surgery, in four out of six patients in whom ERFs were recordable, M400 at the anterior temporal channels on the resected side disappeared, and the activity in the affected mesial temporal area was lost. In one patient who underwent inferior lateral temporal resection, M400 waveforms and its sources were preserved in all regions. There were no significant differences in the latency and dipole moments of the unaffected source of M400 before versus after surgery. These results suggest that the hippocampus contributes to the scalp-recorded P300 only at the corresponding anterior temporal region, and does not influence its general waveform and predominant distribution over the scalp.

Adult↗
PubMed1999

Focal ictal direct current shifts in human epilepsy as studied by subdural and scalp recording.

In order to clarify further the characteristics of ictal direct current (DC) shifts in human epilepsy, we investigated them by subdural and scalp recording in six and three patients, respectively, both having mainly neocortical lobe epilepsy (five with frontal lobe epilepsy, two with parietal lobe epilepsy and two with temporal lobe epilepsy). By using subdural electrodes made of platinum, ictal DC shifts were observed in 85% of all the recorded seizures (89 seizures) among the six patients, and they were localized to just one or two electrodes at which the conventional initial ictal EEG change was also observed. They were closely accompanied by the electrodecremental pattern in all patients except for one in whom 1 Hz rhythmic activity was superimposed on clear negative slow shifts. Seizure control after resection of the cortex, including the area showing DC shifts, was favourable irrespective of histological diagnosis. Scalp-recorded ictal slow shifts were observed in 23% of all the recorded seizures (60 seizures) among the three patients. They were, like the subdurally recorded ones, mainly surface-negative in polarity, closely related to the electrodecremental pattern and consistent in their location. It seems that scalp-recorded DC shifts were detected particularly when seizures were clinically intense, while no slow shifts were observed in small seizures. It is concluded that at least subdurally recorded ictal slow shifts are clinically useful before epilepsy surgery to delineate more specifically an epileptogenic area as well as to further confirm the conventional initial ictal EEG change, and that scalp-recorded ictal slow shifts also have high specificity although their low sensitivity is to be taken into account.

Adolescent↗
PubMed1999

Cognitive motor control in human pre-supplementary motor area studied by subdural recording of discrimination/selection-related potentials.

To clarify the functional role of human pre-supplementary motor area (pre-SMA) in 'cognitive' motor control as compared with other non-primary motor cortices (SMA-proper and lateral premotor areas) and prefrontal area, we recorded epicortical field potentials by using subdural electrodes in five epileptic patients during presurgical evaluation, whose pre-SMA, SMA-proper, prefrontal and lateral premotor areas were defined by electric cortical stimulation and recent anatomical orientations according to the bicommissural plane and callosal grid system. An S1-Go/NoGo choice and delayed reaction task (S1-choice paradigm) and a warned choice Go/NoGo reaction task (S2-choice paradigm) with inter-stimulus intervals of 2 s were employed. The results showed (i) transient potentials with onset and peak latencies of about 200 and 600 ms, respectively, after S1 in the S1-choice paradigm mainly at pre-SMA and to a lesser degree at the prefrontal and lateral premotor areas, but not in the S2-choice paradigm. At SMA-proper, a similar but much smaller potential was seen after S1 in both S1- and S2-choice paradigms and (ii) slow sustained potentials between S1 and S2 in both S1- and S2-choice paradigms in all of the non-primary motor areas investigated (pre-SMA, SMA-proper and lateral premotor areas) and prefrontal area. It is concluded that pre-SMA plays a more important role in cognitive motor control which involves sensory discrimination and decision making or motor selection for the action after stimuli, whereas SMA-proper is one of the main generators of Bereitschaftspotential preceding self-paced, voluntary movements. In the more general anticipation of and attention to the forthcoming stimuli, non-primary motor cortices including pre-SMA, SMA-proper and lateral premotor area, and the prefrontal area are commonly involved.

Adult↗
PubMed1999

Abnormal cortical processing of voluntary muscle relaxation in patients with focal hand dystonia studied by movement-related potentials.

In order to clarify the abnormality in cortical motor preparation for voluntary muscle relaxation of the hand in patients with focal hand dystonia, Bereitschaftspotentials (BPs) preceding voluntary muscle contraction and relaxation were recorded in eight patients (three with simple writer's cramp and five with dystonic writer's cramp), and were compared with those from 10 normal subjects. Voluntary muscle relaxation: after keeping the right wrist in an extended position for > 5 s, the subject let the hand drop by voluntarily terminating muscle contraction of the wrist extensor without any associated muscle contraction. Voluntary muscle contraction: the right wrist was flexed by voluntarily contracting the wrist flexor muscle. Scalp EEGs were recorded from 11 electrodes placed over the frontal, central and parietal areas. In the control group, the BP measured at the movement onset was maximal at the left central area (C1), and distributed predominantly over the left hemisphere equally in both the contraction and relaxation tasks. In the focal hand dystonia group, BP was maximal at C1 in the contraction task, whereas, in the relaxation task, it was maximal at the midline central area (Cz) and symmetrically distributed. At the left central area, the BP amplitude in the focal hand dystonia group was diminished significantly in the relaxation task compared with the contraction task (P < 0.05). The present results demonstrate for the first time that the cortical preparatory process for voluntary muscle relaxation, or motor inhibition, is abnormal in focal hand dystonia.

Adult↗
PubMed1999

Induction of apoptosis signal regulating kinase 1 (ASK1) after spinal cord injury in rats: possible involvement of ASK1-JNK and -p38 pathways in neuronal apoptosis.

The aims of this study were to clarify the mechanism of cell death by apoptosis in the spinal cord after traumatic injury, and to examine the role of the mitogen-activated protein kinase (MAPK) pathways in the transmission of apoptosis signals. The rat spinal cord, experimentally injured by extradural static weight-compression, was studied by hematoxylin and eosin staining, Nissl-staining, terminal deoxynucleotidyl transferase (TdT) mediated dUTP nick-end labeling (TUNEL) staining, and immunostaining using polyclonal antibodies against Apoptosis Signal-regulating Kinase 1 (ASK1), c-Jun N-terminal kinase (JNK), and p38 MAPK. TUNEL-positive cells were present at all stages studied until 7 days after injury, and percentage positivity for these cells was maximal at 3 days after injury. Electron microscopic analysis revealed the occurrence of apoptosis in both neuronal cells and glial cells. TUNEL-positive glial cells were stained by oligodendrocyte-specific maker. Expression of ASK1 was maximal at 24 h after injury in the gray matter and at 3 days after injury in the white matter. Following the expression of ASK1, activated forms of JNK and p38 were observed in apoptotic cells detected by the TUNEL method. Colocalization of ASK1 and activated JNK or activated p38 was observed in the same cell. These findings suggest the involvement of the stress-activated MAPK pathways including ASK1 in the transmission of apoptosis signals after spinal cord injury.

Animals↗
PubMed1999

Prevalence of hepatitis G virus in liver disease.

The prevalence of hepatitis G virus (HGV) in liver disease of non-A, -B, -C viral hepatitis, hepatitis B and hepatitis C was determined. Two of 44 patients (4.5%) with liver injury without any hepatitis A, B or C marker were positive for HGV. One of five cases of hepatocellular carcinoma was positive for HGV. One of three cases with fulminant hepatitis was positive for HGV. This case was negative at the onset of fulminant hepatitis and became positive after plasmapheresis. No patient with acute (n=8) or chronic (n=5) hepatitis or liver cirrhosis (n=8) was positive for HGV in non-A, -B, -C liver disease. One of 30 patients with various HBV-positive liver diseases and nine (17.3) of 52 patients with type C liver disease were positive for HGV. In patients with hepatitis C, four (28.6%) of 14 HGV-co-infected patients were complicated with diabetes mellitus compared with four (10.5%) of 38 single hepatitis C virus (HCV)-infected patients (not significant). In 12 HGV-positive patients, eight of 10 (80%) had a history of blood transfusion. In HCV-positive patients, co-infection with HGV was not a risk factor in patients with diabetes mellitus as a complication. HGV appeared to cause non-A, -B, -C hepatitis rarely, and its main route of infection was blood transfusion.

Adolescent↗
PubMed1999

Localization of Smads, the TGF-beta family intracellular signaling components during endochondral ossification.

Members of the transforming growth factor-beta (TGF-beta) family transduce signals from the cell membrane to the nucleus via specific type I and type II receptors and Smad proteins. Smad1 and Smad5 mediate intracellular signaling of bone morphogenetic protein (BMP), whereas Smad2 and Smad3 transduce TGF-beta signaling. Smad4 is a common mediator required for both pathways. Smad6 and Smad7 inhibit signaling by members of the TGF-beta superfamily. Here, we examined the expression of Smad1 to Smad7 proteins during endochondral ossification of epiphyseal plate of growing rats using immunohistochemical techniques. The expression of Smad proteins was correlated with the expression of TGF-beta1 and its receptors, and BMP-2/4 and BMP receptors. The results show that TGF-beta1 and BMP-2/4 were actively expressed in chondrocytes that are undergoing proliferation and maturation, which overlaps with expression of their corresponding type I and type II receptors. The Smads, however, exhibited a distinct expression pattern, respectively. For example, Smad1 and Smad5 were highly expressed in proliferating chondrocytes and in those chondrocytes that are undergoing maturation. The TGF-beta/activin-restricted Smads were also expressed in a nearly complementary fashion; Smad2 was strongly expressed in proliferating chondrocytes, whereas Smad3 was strongly observed in maturing chondrocytes. Smad4 was broadly expressed in all zones of epiphyseal plate. Inhibitory Smads, Smad6 and Smad7, were strongly expressed in the zone of cartilage that contained mature chondrocytes. Our findings show a colocalization of the pathway-restricted and inhibitory Smads with activating ligands or ligands whose action they antagonize and their receptors in various zones of epiphyseal growth plate, suggesting that TGF-beta superfamily Smad signaling pathways plays a morphogenic role during endochondral bone formation.

Activin Receptors, Type I↗
PubMed1999

Apoptosis following spinal cord injury in rats and preventative effect of N-methyl-D-aspartate receptor antagonist.

OBJECT: The aims of this study were to clarify the histological and histochemical changes associated with cell death in the spinal cord after acute traumatic injury and to examine the role of excitatory amino acid release mediated by N-methyl-D-aspartate (NMDA) receptors. METHODS: Following laminectomy, the spinal cord in 70 rats was injured at the T-9 level by applying extradural static weight-compression, in which a cylindrical compressor was used to induce complete and irreversible transverse spinal cord injury (SCI) with paralysis of the lower extremities. The injured rats were killed between 30 minutes and 14 days after injury, and the injured cord was removed en bloc. Rats that received NMDA receptor antagonist (MK-801) were killed at the same time points as those that received saline. The specimens were stained with hematoxylin and eosin, Nissl, and Klüver-Barrera Luxol fast blue and subjected to in situ nick-end labeling, a specific in situ method used to allow visualization of apoptosis. Thirty minutes post-SCI, a large hematoma was observed at the compressed segment. Six hours after injury, large numbers of dead cells that were not stained by in situ nick-end labeling were observed. Between 12 hours and 14 days postinjury, nuclei stained by using the in situ nick-end labeling technique were observed not only at the injury site but also in adjoining segments that had not undergone mechanical compression, suggesting that the delayed cell death was due to apoptosis. The number of cells stained by in situ nick-end labeling was maximum at 3 days postinjury. The results of electron microscopic examination were also consistent with apoptosis. In the MK-801-treated rats, the number of cells stained by in situ nick-end labeling was smaller than in nontreated rats at both 24 hours and 7 days after injury. CONCLUSIONS: These findings suggest that NMDA-receptor activation promotes delayed neuronal and glial cell death due to apoptosis.

Animals↗
PubMed1999

[Functional localization of the somatomotor area by magnetoencephalography].

Precise localization of the current dipole by the magnetoencephalography (MEG) has enabled us to combine the functional information onto the anatomical landmarks. This merit can be best exhibited when the dipole is situated in the superficial cortex and directed parallel to the skull surface. However, before utilizing MEG extensively as a clinical tool, it is inevitable to confirm the precision of the source localization by comparing the estimation with the actual sources. Somatosensory evoked field (SEF) following the electric shock to the peripheral nerve and movement-related cortical field (MRCF) associated with self-paced movement can show us the estimated sources at the postcentral and precentral cortex, respectively, with somatotopic organization. These localizations were confirmed by the direct recordings from the human brain surface during the operation, even if the corresponding areas were anatomically distorted by some lesion occupying the central area. In addition, MEG can localize second somatosensory area (SII) over the superior bank of the Sylvian fissure as well as posterior parietal cortex (PPC), which are difficult to be detected by the EEG recording. These reliable estimation enables us to apply MEG to clarification of pathogenesis of various diseases and source localization for higher brain function.

Evoked Potentials, Somatosensory↗
PubMed1999

Clonic convulsion caused by epileptic discharges arising from the human supplementary motor area as studied by subdural recording.

In order to help clarify the mechanism of tonic convulsion, which is commonly seen in supplementary motor area (SMA) seizures, we investigated the temporal relationship between ictal discharges arising from the SMA and the associated EMG discharges in the foot, in a patient with SMA seizures, prior to surgical treatment. The patient's intractable seizures consisted of tonic followed by clonic convulsion of the left foot also involving at times, the left hand. Ictal EEGs were investigated by subdural electrodes placed on the SMA-proper and pre-SMA, which were defined by cortical stimulation and by recording cortical-evoked potentials. Interictally, repetitive spike discharges were seen at the pre-SMA. Each seizure initially had a tonic phase associated with an electrodecremental EEG pattern. It was followed by clonic convulsion as shown by clonic EMG discharges of the left tibialis anterior (TA) muscle. It had a duration of 300 to 500 msec, and on each occasion a positive cortical activity at the pre-SMA preceded the EMG onset by 110 msec, and a negative spike at the SMA-proper preceded the EMG onset by 50 to 60 msec. Epileptic discharges originating from the pre-SMA spread to the SMA-proper and possibly also to the primary motor cortex (MI) in this patient. Since both SMA-proper and MI could elicit EMG discharges through the independent corticospinal tracts having different conduction velocities, even a single spike arising from the SMA could give rise to a long EMG burst, which may play some role in the tonic convulsion which characterizes SMA seizures.

Adult↗
PubMed1998

Influence of unilateral deafness on auditory evoked magnetic field.

To investigate the effect of unilateral deafness on central auditory mechanisms, we examined patients with unilateral deafness of various durations. Auditory evoked magnetic fields (AEF) were recorded using a whole-head neuromagnetometer. In patients who had unilateral deafness for more than 3 weeks, the average N100m latency in the ipsilateral hemisphere did not differ from that in the contralateral hemisphere. In addition, in some patients with congenital or early onset deafness, the equivalent current dipole (ECD) moment was larger in the ipsilateral hemisphere than in the contralateral hemisphere. These findings suggest that unilateral deafness may cause reorganization of the central auditory pathway. They also suggest that central auditory pathway in adults has some plasticity, though not as much as in childhood.

Adult↗