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PubMed1983

Studies on the mechanism of antiaggregatory effect of Moutan Cortex.

The effects of Moutan Cortex and one of its major components, paeonol, on platelet aggregation and arachidonic acid (AA) metabolism in human platelets were studied. One week oral administration of water extract of Moutan Cortex [Moutan Cortex (w), 3 g/day] significantly reduced platelet aggregation and thromboxane B2 (TXB2) formation induced by collagen, epinephrine and ADP. Paeonol dose-dependently inhibited ADP and collagen induced platelet aggregation in vitro. Moutan Cortex (w) and paeonol dose-dependently inhibited the conversion of exogenous [14C]AA to [14C]heptadecatetraenoic acid [( 14C]HHT) and [14C]TXB2 by washed human platelets, while both of them increased its conversion to [14C]12-hydroxy eicosatetraenoic acid [( 14C]12-HETE). High dose of Moutan Cortex (w) inhibited the release of [14C]AA from prelabeled platelets in vitro, while paeonol did not. These results suggest that a reduction in platelet aggregation by the oral administration of Moutan Cortex might be ascribed to a decrease in thromboxane synthesis and that paeonol might play an important role in the antiaggregatory effect of Moutan Cortex because of its potent inhibitory effect on platelet aggregation and thromboxane formation.

Acetophenones↗

PubMedDate not supplied

Influence of ipsilateral lesions of the nucleus basalis magnocellularis and of choline alphoscerate treatment on histochemically reactive zinc stores and on the ultrastructure of the rat frontal cortex.

The influence of ipsilateral lesions of the nucleus basalis magnocellularis (NBM) and of choline alphoscerate treatment on histochemically reactive zinc stores and on the ultrastructure of the neuropil of layer III of the frontal cortex were investigated in the rat. In control animals a dark-brown staining was developed in the neuropil of layers I-III of the frontal cortex. Lesions of the right NBM caused a marked reduction in the density of sulphide-silver staining in the right frontal cortex 4 weeks post lesion. Moreover, changes in the morphology and in the density of synaptic buttons in the neuropil of layer III of the cerebral cortex were also noticeable. Concomitant treatment for 4 weeks with choline alphoscerate restored the density of sulphide-silver staining in the right frontal cortex and countered in part changes of synaptic buttons of the neuropil of layer III of the frontal cortex. These findings suggest that the loss of cerebrocortical histochemically reactive zinc stores occurring in NBM-lesioned rats is due to the alterations of synaptic contacts in the frontal cortex and that treatment with choline alphoscerate may counter these degenerative changes.

Journal Article↗

PubMed2004

Protective effect of Moutan Cortex extract on acetaminophen-induced hepatotoxicity in mice.

Previously, we demonstrated that Moutan Cortex prevents acetaminophen (AAP)-induced cytotoxicity in vitro. The present study examined the protective effect of Moutan Cortex on AAP induced hepatotoxicity and the possible mechanisms underlying this effect in mice. When Montan Cortex was administered to ICR mice, followed by hepatotoxic dose of AAP (400 mg/kg, i.p.), Moutan Cortex pre-exposure prevented liver injury as indicated by the decrease of serum alanine aminotransferase level. Moutan Cortex also protected AAP-induced hepatic glutathione depletion. Cytochrome P450 2E1-dependent aniline and p-nitrophenol hydroxylases activities in microsomal incubations were significantly inhibited by Moutan Cortex. Abrogation of toxicity was also mirrored in DNA fragmentation. These observations demonstrate that Moutan Cortex pre-exposure may attenuate AAP-induced GSH depletion, cytochrome P450 2E1 activity, and hepatic DNA damage in vivo.

Acetaminophen↗

PubMed2005

Distributions of transmitter receptors in the macaque cingulate cortex.

The primate cingulate cortex is structurally and functionally complex. Although no studies have investigated the regional densities of multiple neurotransmitter receptor systems, such information would be useful for assessing its functions and disease vulnerabilities. We quantified nine different receptors in five transmitter systems by in vitro autoradiographic mapping of the cingulate cortex of macaque monkeys with the aim to link cytoarchitectonic regions and functional specialization. Receptor mapping substantiated the subdivision of the cingulate cortex into anterior versus posterior regions. In anterior cingulate cortex (ACC) AMPA glutamatergic receptors and GABA(A) inhibitory receptors were present in significantly higher concentrations than the modulatory alpha-adrenergic and muscarinic receptors. These differences were absent in the posterior cingulate cortex (PCC). By contrast, NMDA receptor densities were significantly higher than AMPA receptor densities in PCC, but not in ACC. The midcingulate area 24' shared more features with ACC than PCC. This area was characterized by the highest ratios of NMDA receptors to alpha-adrenergic, muscarinic and 5-HT2 receptors among all cingulate regions. Compared to rostrocaudal divisions, the differences between dorsoventral subdivisions a-c were small in all regions of cingulate cortex, and only muscarinic and alpha-adrenergic receptor densities followed the degree of cytoarchitectonic differentiation. We conclude that multiple receptor mapping reveals a highly differentiated classification of cingulate cortex with a characteristic predominance of fast ionotropic excitatory and inhibitory receptors in ACC, but a strong and varied complement of NMDA and metabotropic receptors in PCC.

Animals↗

PubMed2006

Visuo-motor integration and control in the human posterior parietal cortex: evidence from TMS and fMRI.

The posterior parietal cortex is a fundamental structure for visuo-motor integration and control. Here I discuss recent transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) studies that I interpret as suggesting four concepts. The evolutionary process has enlarged the human posterior parietal cortex while still preserving the internal structure of the posterior parietal cortex of other primates. Visuo-motor control in the posterior parietal cortex may be implemented by coding primarily action goals. The lateralization of visuo-motor functions in the posterior parietal cortex suggests that the left posterior parietal cortex is more concerned with tool use and the right posterior parietal cortex is more concerned with imitation of the actions of others. Finally, visuo-motor inter-hemispheric transfer through parietal callosal fibers occurs at the level of 'motor intention'.

Brain Mapping↗

PubMed2005

Infralimbic cortex activation increases c-Fos expression in intercalated neurons of the amygdala.

Recently, it was reported that stimulation of the infralimbic cortex produces a feedforward inhibition of central amygdala neurons. The interest of this observation comes from the fact that the central nucleus is the main output station of the amygdala for conditioned fear responses and evidence that the infralimbic cortex plays a critical role in the extinction of conditioned fear. However, the identity of the neurons mediating this infralimbic-evoked inhibition of the central nucleus remains unknown. Likely candidates are intercalated amygdala neurons. Indeed, these cells receive glutamatergic afferents from the infralimbic cortex, use GABA as a transmitter, and project to the central amygdala. Thus, the present study was undertaken to test whether, in adult rats, the infralimbic cortex can affect the activity of intercalated neurons. To this end, disinhibition of the infralimbic cortex was induced by local infusion of the non-competitive GABA-A receptor antagonist picrotoxin. Subsequently, neuronal activation was determined bilaterally within the amygdala using induction of the immediate early gene Fos. Infralimbic disinhibition produced a significant increase in the number of Fos-immunoreactive intercalated cells bilaterally whereas no change was detected in the central nucleus. In the basolateral amygdaloid complex, increases in the number of Fos-immunoreactive cells only reached significance in the contralateral lateral nucleus. These results suggest that glutamatergic inputs from the infralimbic cortex directly activate intercalated neurons. Thus, our findings raise the possibility that the infralimbic cortex inhibits conditioned fear via the excitation of intercalated cells and the consequent inhibition of central amygdala neurons.

Amygdala↗

PubMed2004

The functional neuroanatomy of the human orbitofrontal cortex: evidence from neuroimaging and neuropsychology.

The human orbitofrontal cortex is an important brain region for the processing of rewards and punishments, which is a prerequisite for the complex and flexible emotional and social behaviour which contributes to the evolutionary success of humans. Yet much remains to be discovered about the functions of this key brain region, and new evidence from functional neuroimaging and clinical neuropsychology is affording new insights into the different functions of the human orbitofrontal cortex. We review the neuroanatomical and neuropsychological literature on the human orbitofrontal cortex, and propose two distinct trends of neural activity based on a meta-analysis of neuroimaging studies. One is a mediolateral distinction, whereby medial orbitofrontal cortex activity is related to monitoring the reward value of many different reinforcers, whereas lateral orbitofrontal cortex activity is related to the evaluation of punishers which may lead to a change in ongoing behaviour. The second is a posterior-anterior distinction with more complex or abstract reinforcers (such as monetary gain and loss) represented more anteriorly in the orbitofrontal cortex than simpler reinforcers such as taste or pain. Finally, we propose new neuroimaging methods for obtaining further evidence on the localisation of function in the human orbitofrontal cortex.

Brain Mapping↗

PubMed2000

Diazepam attenuation of somatostatin binding and effect of somatostatin on accumulation of inositol 1,4,5-trisphosphate in the rat frontoparietal cortex.

Numerous reports in both humans and animals have confirmed that benzodiazepines produce amnesia; however, mechanisms mediating this effect are not clear. In view of the important role of brain somatostatin (SRIF) in the cognitive function of rats, this study sought to determine if the benzodiazepine, diazepam, alters somatostatinergic system in the rat frontoparietal cortex. Intraperitoneal (i.p.) administration of diazepam (5 mg/kg/day) to male Wistar rats (200-250 g) for 3 or 7 days decreased the number of SRIF receptors (26 and 37%, respectively) in synaptosomes from the frontoparietal cortex, without influencing their apparent affinity. This decrease in the tracer binding was not attributable to a direct effect of diazepam on SRIF receptors, because no decrease of SRIF binding was induced by a large concentration of diazepam (10(-4) M) when the drug was added to a preparation of synaptosomes from frontoparietal cortex of untreated rats. To determine if the effect of diazepam on SRIF binding is related to the binding of diazepam to its recognition site on the GABA(A) receptor, a benzodiazepine antagonist, 2-phenylpyrazolo[3,4-c]quinolin-3(5H)-one (CGS 8216) was administered before the diazepam injection. Pretreatment with CGS 8216 (20 mg/kg/day, i.p.) blocked completely the diazepam-induced decrease in the number of SRIF receptors. CGS 8216 alone had no observable effect. The decrease in the number of 125I-Tyr11-SRIF receptor induced by diazepam was accompanied by a decrease in the effect of SRIF, after 15 seconds of stimulation, on inositol 1,4, 5-trisphosphate (IP3) mass accumulation in the rat frontoparietal cortex at 3 (64%) or 7 days (59%) after its administration. Diazepam alone had no observable effect on mass accumulation of IP3. After 14 days of daily diazepam injections, the levels of binding of 125I-Tyr11-SRIF in the frontoparietal cortex returned to control values, coinciding with the tolerance that develops to this benzodiazepine agonists when administered chronically. The decrease in IP3 levels was still observed after 14 days (57%) diazepam administration. Diazepam and CGS 8216 did not affect SRIF-like immunoreactivity levels in the frontoparietal cortex at the three time intervals studied (3, 7 or 14 days). The alteration of frontoparietal cortex SRIF receptor-effector system after 3 or 7 days of diazepam treatment suggests that somatostatinergic neurotransmission plays a role in the mechanism of diazepam action on memory.

Animals↗

PubMed2001

Low GSK-3 activity in frontal cortex of schizophrenic patients.

Glycogen synthase kinase-3 (GSK-3) (EC 2.7.1.37) is a protein kinase highly abundant in brain and involved in signal transduction cascades of multiple cellular processes, particularly neurodevelopment. Two forms of the enzyme, GSK-3alpha and -3beta have been previously identified. We have previously reported reduced GSK-3beta protein levels in postmortem frontal cortex of schizophrenic patients. In an attempt to explore whether reduction of GSK-3beta levels is brain region specific we examined it in occipital cortex. In order to find out if the reduction in frontal cortex is reflected in altered activity we measured GSK-3 enzymatic activity in this brain region. Western-blot analysis of GSK-3beta was carried out in postmortem occipital cortex of 15 schizophrenic, 15 bipolar, and 15 unipolar patients, and 15 normal controls. GSK-3 activity was measured by quantitating the phosphorylation of the specific substrate phospho-CREB in the frontal cortex specimens. GSK-3beta levels in occipital cortex did not differ between the four diagnostic groups. GSK-3 activity in the frontal cortex of schizophrenic patients was 45% lower than that of normal controls (0.196+/-0.082 and 0.357+/-0.084 pmol/mg proteinxmin, respectively; Kruskal-Wallis analysis: chi-square=8.27, df=3, p=0.04). The other two diagnostic groups showed no difference from the control group. Our results are consistent with the notion that schizophrenia involves neurodevelopmental pathology.

Bipolar Disorder↗

PubMed2001

Impairments in visual discrimination learning and recognition memory produced by neurotoxic lesions of rhinal cortex in rhesus monkeys.

Much work on the cognitive functions of the primate rhinal (i.e. entorhinal plus perirhinal) cortex has been based on aspiration lesions of this structure, which might disrupt fibres passing nearby and through the rhinal cortex in addition to removing the cell bodies of the rhinal cortex itself. To determine whether damage limited to the cell bodies of the rhinal cortex is sufficient to impair visual learning and memory, four rhesus monkeys (Macaca mulatta) were preoperatively trained on a battery of visual learning and memory tasks, including single-pair discrimination learning for primary reinforcement, single-pair discrimination reversals, concurrent discrimination learning and reversal, and delayed matching-to-sample. Following acquisition of these tasks and a preoperative performance test, ibotenic acid was injected bilaterally into the rhinal cortex, and the monkeys were retested. Consistent with the results of studies using aspiration lesions, the monkeys were impaired on single-pair discrimination learning as well as recognition memory performance postoperatively, although reliable reversal learning impairments were not observed. The magnitude of postoperative impairment in discrimination learning was not correlated with the magnitude of postoperative impairment in recognition memory, suggesting a possible dissociation between these functions within the rhinal cortex. The correspondence of behavioural deficits following aspiration and neurotoxic lesions of the rhinal cortex validates the attribution of various cognitive functions to this structure, based on the results of studies with aspiration lesions.

Animals↗

PubMedDate not supplied

The perceptual-mnemonic/feature conjunction model of perirhinal cortex function.

The perirhinal cortex was once thought to be "silent cortex", virtually ignored by researchers interested in the neurobiology of learning and memory. Following studies of brain damage associated with cases of amnesia, perirhinal cortex is now widely regarded as part of a "medial temporal lobe (MTL) memory system". This system is thought to be more or less functionally homogeneous, having a special role in declarative memory, and making little or no contribution to other functions such as perception. In the present article, we summarize an alternative view. First, we propose that components of the putative MTL system such as the hippocampus and perirhinal cortex have distinct and dissociable functions. Second, we provide evidence that the perirhinal cortex has a role in visual discrimination. In addition, we propose a specific role for perirhinal cortex in visual discrimination: the contribution of complex conjunctive representations to the solution of visual discrimination problems with a high degree of "feature ambiguity". These proposals constitute a new view of perirhinal cortex function, one that does not assume strict modularity of function in the occipito-temporal visual stream, but replaces this idea with the notion of a hierarchical representational continuum.

Animals↗

PubMed2006

Reassembly of contractile actin cortex in cell blebs.

Contractile actin cortex is involved in cell morphogenesis, movement, and cytokinesis, but its organization and assembly are poorly understood. During blebbing, the membrane detaches from the cortex and inflates. As expansion ceases, contractile cortex re-assembles under the membrane and drives bleb retraction. This cycle enabled us to measure the temporal sequence of protein recruitment to the membrane during cortex reassembly and to explore dependency relationships. Expanding blebs were devoid of actin, but proteins of the erythrocytic submembranous cytoskeleton were present. When expansion ceased, ezrin was recruited to the membrane first, followed by actin, actin-bundling proteins, and, finally, contractile proteins. Complete assembly of the contractile cortex, which was organized into a cagelike mesh of filaments, took approximately 30 s. Cytochalasin D blocked recruitment of actin and alpha-actinin, but had no effect on membrane association of ankyrin B and ezrin. Ezrin played no role in actin nucleation, but was essential for tethering the membrane to the cortex. The Rho pathway was important for cortex assembly in blebs.

Actins↗

PubMedDate not supplied

Development of inferior temporal cortex in the monkey.

Inferior temporal (IT) cortex is critical for visual pattern recognition in adult primates. However, the functional development of IT cortex appears to be incomplete until late in the first year of life in monkeys and probably beyond. Responses of neurons in IT are substantially weaker, of longer latency, and more susceptible to anesthesia within at least the first half year of life. In addition, refinement of connections of IT, particularly those with regions in the opposite hemisphere and with regions related to memory and attention, continues for at least several months after birth. Moreover, many of the pattern recognition functions that IT supports in adulthood themselves show a very protracted period of development, and damage to IT cortex in infancy appears to have relatively little effect on pattern recognition abilities, despite the pronounced effects of comparable damage in adulthood. These findings all suggest that IT undergoes an extended period of postnatal development, during which both visual experience and the maturation of other brain structures may contribute to the emergence of mechanisms of pattern recognition within IT. In other respects, fundamental characteristics of IT emerge quite early. For example, despite their weaker responses, IT neurons have adult-like patterns of responsiveness--including pronounced form selectivity and large bilateral receptive fields--as early as we were able to test (approximately 6 weeks). Thus, IT cortex appears to be prewired with (or predisposed to develop rapidly) neural circuitry sufficient to produce basic properties remarkably similar to those found in the adult animal. Future studies of IT cortex will need to address the development of signals related to perceptual constancies and to formation and retrieval of visual object memories, the development of interactions with other regions involved in visual recognition (particularly frontal cortex), and the specific mechanisms underlying various types of plasticity present in IT cortex in both developing and mature primates.

Animals↗

PubMedDate not supplied

Encoding of intention and spatial location in the posterior parietal cortex.

The posterior parietal cortex is functionally situated between sensory cortex and motor cortex. The responses of cells in this area are difficult to classify as strictly sensory or motor, since many have both sensory- and movement-related activities, as well as activities related to higher cognitive functions such as attention and intention. In this review we will provide evidence that the posterior parietal cortex is an interface between sensory and motor structures and performs various functions important for sensory-motor integration. The review will focus on two specific sensory-motor tasks--the formation of motor plans and the abstract representation of space. Cells in the lateral intraparietal area, a subdivision of the parietal cortex, have activity related to eye movements the animal intends to make. This finding represents the lowest stage in the sensory-motor cortical pathway in which activity related to intention has been found and may represent the cortical stage in which sensory signals go "over the hump" to become intentions and plans to make movements. The second part of the review will discuss the representation of space in the posterior parietal cortex. Encoding spatial locations is an essential step in sensory-motor transformations. Since movements are made to locations in space, these locations should be coded invariant of eye and head position or the sensory modality signaling the target for a movement. Data will be reviewed demonstrating that there exists in the posterior parietal cortex an abstract representation of space that is constructed from the integration of visual, auditory, vestibular, eye position, and proprioceptive head position signals. This representation is in the form of a population code and the above signals are not combined in a haphazard fashion. Rather, they are brought together using a specific operation to form "planar gain fields" that are the common foundation of the population code for the neural construct of space.

Animals↗

PubMedDate not supplied

Prenatal development of NADPH-diaphorase-reactive neurons in human frontal cortex.

Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry was used to study the morphology and development of neurons that metabolize nitric oxide (NO) in the frontal cortex of human fetuses aged from 13 weeks of gestation (13W) to term, to investigate whether the two distinct types of NO neuron described in the adult develop differently. Large, heavily stained, sparsely spiny, non-pyramidal neurons (Type I) develop by 15W mainly in the subplate (SP) of the cortical Anlage. They achieve an adult-like pattern by 32W, distributed thoughout the cortex and subcortical white matter, but with the highest concentration in the white matter. Small, lightly stained cells (Type II) develop later (32W) thoughout the cortex, but especially in layers II-IV, and increase in number to term. NADPH-d-positive dendrites and axons appear in the cortex and white matter by 15W. They include thick, radially oriented, dendritic processes from Type I neurons in SP and CP. Their arbors expand and mature between 17 and 28W. Fine horizontal axons are visible in layer I by 17W. Others develop in layers II-IV from 28W, and have reached a high degree of development by term. NADPH-d-positive axons in the cortex seem to have both intrinsic and extrinsic origins. Thus the two types of NADPH-d neurons found in adult primate, including human, cortex are reflected by different developmental forms prenatally. It is concluded that NO-metabolizing neurons in the human cortex may be involved in various aspects of development, including morphological and functional maturation, and that the late-developing Type II neurons may represent a cell line specific to primates, perhaps related to the development of their higher cortical activity and of potential importance in the pathophysiology of diseases of cognitive function.

Embryonic and Fetal Development↗

PubMed1997

The cortex-medulla oocyte growth pattern is organized during fetal life: an in-vitro study of the mouse ovary.

The cortex-medulla growth pattern of oocytes in the developing ovary is formed by a rim of small non-growing oocytes at the periphery and growing oocytes at the inner part of the cortex and in the medulla. In this study we aimed to: (i) develop an in-vitro model using fetal mouse ovaries to evaluate when the cortex-medulla growth pattern is organized during ovarian differentiation; and (ii) study the interaction between small, non-growing and growing oocytes. Fetal mouse ovaries of days 11, 13 and 16 post coitus (E11, E13 and E16) were cultured for 14, 12 and 9 days respectively, corresponding to post-partum day 7 (P7). A cortex-medulla growth pattern had developed by P7 in most ovaries from E16 and in half of those from E13. No ovaries from E11 developed a cortex-medulla pattern. The organization of this pattern within the ovary is concurrent with the initiation of meiosis. Ovaries with a cortex-medulla growth pattern had the same number of growing follicles (approximately 87), regardless of the number of small, non-growing oocytes present. In contrast, in most ovaries without a cortex-medulla pattern, almost all oocytes began to grow. Hence, the geographically determined growth pattern of oocytes in the developing mouse ovary may be organized at the onset of meiosis and is sustained by a balanced interaction between small and growing follicles.

Animals↗

PubMed2001

Structural features and thickness of the vertebral cortex in the thoracolumbar spine.

STUDY DESIGN: The thickness and structure of the vertebral body cortex were examined from sections of human cadaveric vertebrae. OBJECTIVES: The objectives were to identify the principal structural features of the cortex, to directly measure the minimum and maximum thicknesses of the cortex in the thoracolumbar spine, and to compare regional variations in the structure of the cortex. SUMMARY OF BACKGROUND DATA: The thickness of the vertebral cortical shell contributes to the compressive strength of the vertebral body. There is little consensus concerning the thickness and morphology of vertebral shell and endplate along the spine in existing data. METHODS: Human T1, T5, T9, L1, and L5 vertebral bodies (mean age 70.4 years) from 20 cadaveric spines were sectioned and photographed. The minimum and maximum cortical thickness of the shells and endplates in the midsagittal plane were measured from magnified images. RESULTS: The anterior shell thickness was significantly greater than the posterior shell and both endplates. Endplate thickness was greatest in the lower lumbar vertebrae. There was a significant decrease in cortex thickness over the central portion of endplates and shells, with a mean minimum thickness of 0.40 mm and a mean maximum thickness of 0.86 mm, with an overall mean of 0.64 +/- 0.41 mm. Increased porosity was also observed along the central regions of the cortical shells. In the lower thoracic and lumbar spine, a double-layered endplate structure was observed. CONCLUSIONS: Invasive techniques provide the only means to directly resolve the thickness and distribution of bone in the vertebral cortex. The cortex thickness and structure varies along the endplates and the anterior and posterior surfaces of the vertebral body. The implications of the so called double-layered endplate structure are unknown, but indicate the need for further study.

Aged↗

PubMed2002

Mastoid cortex plasty using bone pate.

OBJECTIVE: To describe the surgical technique of mastoid cortex plasty using bone pate and its clinical significance. STUDY DESIGN: Retrospective. SETTING: Tertiary medical center. METHODS: Bone pate collected while drilling the mastoid cortex was mixed with fibrin glue to make a pate plate. The mastoid cortex defect was closed with a pate plate cut to the desired shape and size. PATIENTS AND MAIN OUTCOME MEASURES: Mastoid cortex plasty was included in the first-stage operation in 49 patients who underwent staged tympanoplasty. The second-stage operation was an inspection to see whether the mastoid cortex was reconstructed and the ingrowth of fibrous soft tissue was prevented. RESULTS: In 35 patients, the mastoid cortex was reconstructed completely, and soft tissue ingrowth into the mastoid cavity was blocked completely. In the remaining 14 patients, a defect of varying size occurred at the site of drainage-tube insertion. This defect was small enough to prevent soft tissue ingrowth into the mastoid cavity. CONCLUSION: Mastoid cortex plasty is a simple and rapid procedure for preventing postoperative deformity of the mastoid process and is valuable for restoring mastoid cavity function.

Adolescent↗