Longitudinal MRI of the developing ferret brain reveals regional variations in timing and rate of growth.

Normative ferret brain development was characterized using magnetic resonance imaging. Brain growth was longitudinally monitored in 10 ferrets (equal numbers of males and females) from postnatal day 8 (P8) through P38 in 6-d increments. Template T2-weighted images were constructed at each age, and these were manually segmented into 12 to 14 brain regions. A logistic growth model was used to fit data from whole brain volumes and 8 of the individual regions in both males and females. More protracted growth was found in males, which results in larger brains; however, sex differences were not apparent when results were corrected for body weight. Additionally, surface models of the developing cortical plate were registered to one another using the anatomically-constrained Multimodal Surface Matching algorithm. This, in turn, enabled local logistic growth parameters to be mapped across the cortical surface. A close similarity was observed between surface area expansion timing and previous reports of the transverse neurogenic gradient in ferrets. Regional variation in the extent of surface area expansion and the maximum expansion rate was also revealed. This characterization of normative brain growth over the period of cerebral cortex folding may serve as a reference for ferret studies of brain development.

Altered thalamocortical tract trajectory growth with undisrupted thalamic parcellation pattern in human lissencephaly brain at mid-gestational stage.

Proper topographically organized neural connections between the thalamus and the cerebral cortex are mandatory for thalamus function. Thalamocortical (TC) fiber growth begins during the embryonic period and completes by the third trimester of gestation, so that human neonates at birth have a thalamus with a near-facsimile of adult functional parcellation. Whether congenital neocortical anomaly (e.g., lissencephaly) affects TC connection in humans is unknown. Here, via diffusion MRI fiber-tractography analysis of long-term formalin-fixed postmortem fetal brain diagnosed as lissencephaly in comparison with an age-matched normal one, we found similar topological patterns of thalamic subregions and of internal capsule parcellated by TC fibers. However, lissencephaly fetal brain showed white matter structural changes, including fewer/less organized TC fibers and optic radiations, and much less cortical plate invasion by TC fibers - particularly around the shallow central sulcus. Diffusion MRI fiber tractography of normal fetal brains at 15, 23, and 26 gestational weeks (GW) revealed dynamic volumetric change of each parcellated thalamic subregion, suggesting coupled developmental progress of the thalamus with the corresponding cortex. Moreover, from GW23 and GW26 normal fetal brains, TC endings in the cortical plate could be delineated to reflect cumulative progressive TC invasion of cortical plate. By contrast, lissencephaly brain showed a dramatic decrease in TC invasion of the cortical plate. Our study thus shows the feasibility of diffusion MRI fiber tractography in postmortem long-term formalin-fixed fetal brains to disclose the developmental progress of TC tracts coordinating with thalamic and neocortical growth both in normal and lissencephaly fetal brains at mid-gestational stage.

Cone-beam computed tomography assessment of maxillary anterior alveolar bone remodelling in extraction and non-extraction orthodontic cases using stable extra-alveolar reference.

OBJECTIVE: To explore alveolar cortical positional change in response to tooth movement in extraction and non-extraction orthodontic cases, using cone-beam computed tomography (CBCT) and stable extra-alveolar references. MATERIALS AND METHODS: The pre-treatment (T1) and post-treatment (T2) CBCT scans of 25 extraction (EXT) and matched 25 non-extraction (Non-EXT) orthodontic cases were imported into Dolphin Imaging 3D, and oriented uniformly. Sagittal and axial CBCT cross-sections were traced using customized software-generated guides. The displacement of teeth and alveolar bone cortices were automatically measured using the palatal plane (PP) and the line perpendicular to PP and passing Sella as reference. Intra- and inter-group differences between T1 and T2 were analysed. Subjects were also superimposed three-dimensionally using Geomagic Control X for qualitative analysis of cortical remodelling. RESULTS: The EXT group showed incisor retraction, while the Non-EXT group exhibited statistically significant incisor anterior tipping (P < .05). In EXT, both the labial and palatal cortices are resorbed. Non-EXT showed labial cortex anterior modelling, and statistically significant palatal cortex resorption (P < .05). In both groups, statistically significant decrease in total and palatal alveolar widths, increase in labial widths, and palatal dehiscence were observed. Comparatively, EXT showed significantly more incisal total and palatal width decrease and palatal vertical bone loss. CONCLUSION: Labial cortical remodelling was shown to follow anterior tooth movement, but the palatal cortical response to incisor retraction and labial cortical remodelling in general remained inconclusive. Narrowing of the alveolar housing and palatal dehiscence were observed regardless of extraction following orthodontic treatment.

Involvement of strawberry notch homologue 1 in neurite outgrowth of cortical neurons.

When the regulation of axonal and dendritic growth is altered, the neuronal network becomes disordered, which may contribute to the development of psychiatric disorders. Some genome analyses have suggested relationships between mutations in strawberry notch homologue 1 (SBNO1) and neurodevelopmental disorders. However, the function of SBNO1 has not yet been reported. Here, SBNO1 expression pattern during the development of the cerebral cortex in mice was examined. SBNO1 was strongly expressed in the cortical plate and its expression was maintained at a low level during the postnatal stage. CRISPR/Cas9-based knockout of Sbno1 in Neuro2A cultured cells showed delayed growth of neurites. A cortical neuron-specific conditional knockout mouse was constructed, which resulted in hypotrophy of axon bundles and dendrites in cortical neurons. Thus, when mutated, SBNO1 is a candidate gene for psychiatric diseases, such as schizophrenia, as suggested by human genome studies.

Morphological Development Trajectory and Structural Covariance Network of the Human Fetal Cortical Plate during the Early Second Trimester.

During the early second trimester, the cortical plate, or "the developing cortex", undergoes immensely complex and rapid development to complete its major complement of neurons. However, morphological development of the cortical plate and the precise patterning of brain structural covariance networks during this period remain unexplored. In this study, we used 7.0 T high-resolution magnetic resonance images of brain specimens ranging from 14 to 22 gestational weeks to manually segment the cortical plate. Thickness, area expansion, and curvature (i.e., folding) across the cortical plate regions were computed, and correlations of thickness values among different cortical plate regions were measured to analyze fetal cortico-cortical structural covariance throughout development of the early second trimester. The cortical plate displayed significant increases in thickness and expansions in area throughout all regions but changes of curvature in only certain major sulci. The topological architecture and network properties of fetal brain covariance presented immature and inefficient organizations with low degree of integration and high degree of segregation. Altogether, our results provide novel insight on the developmental patterning of cortical plate thickness and the developmental origin of brain network architecture throughout the early second trimester.

Identifying cortical plate inclination as a parameter to re-assess transverse discrepancies in untreated adults with different vertical facial heights-A retrospective CBCT study.

OBJECTIVE: To determine the inclination angles of buccal, palatal cortical plates and assess its harmony with existing molar buccolingual inclination in adults with different vertical facial heights. The aim of this study was to identify the role of cortical plate inclination as a diagnostic tool for determining alveolar support in adults with transverse discrepancies. MATERIALS AND METHODS: One-hundred and fifty seven CBCTs (50-Hypo-divergent, 51-Normo-divergent and 56-Hyper-divergent growth patterns) of untreated adults were utilized. Cross-sectional slices with respect to the maxillary first molar were taken as orientation landmarks in defined reference planes. Inclination angles for the first molar, buccal and palatal cortical plate were determined with respect to the palatal plane. ANOVA and Post Hoc Tukey's HSD test were carried out to determine significant differences between groups. RESULTS: Molar inclination was significantly greater in hyper-divergent groups compared to normo-divergent and hypo-divergent groups (P < .05). Greater variation between molar inclination and cortical plate inclination (buccal and palatal) was seen in hyper-divergent groups (P < .05). Hypo-divergent and normo-divergent groups showed almost similar molar and cortical plate inclinations; however, there was a significant difference between the buccal and palatal cortical plates (P < .05). CONCLUSIONS: Cortical plate inclination is in agreement with molar inclination in hypo- and normo-divergent groups when compared to hyper-divergent groups. In adults with decreased/normal facial heights, greater balance and harmony is observed between the dental and alveolar substructures in the posterior region. In adults with increased facial heights, a greater amount of dentoalveolar compensation is seen with respect to the molar and its surrounding bone support.

Cadmium versus Lanthanum Effects on Spontaneous Electrical Activity and Expression of Connexin Isoforms Cx26, Cx36, and Cx45 in the Human Fetal Cortex.

Electrical activity is important for brain development. In brain slices, human subplate neurons exhibit spontaneous electrical activity that is highly sensitive to lanthanum. Based on the results of pharmacological experiments in human fetal tissue, we hypothesized that hemichannel-forming connexin (Cx) isoforms 26, 36, and 45 would be expressed on neurons in the subplate (SP) zone. RNA sequencing of dissected human cortical mantles at ages of 17-23 gestational weeks revealed that Cx45 has the highest expression, followed by Cx36 and Cx26. The levels of Cx and pannexin expression between male and female fetal cortices were not significantly different. Immunohistochemical analysis detected Cx45- and Cx26-expressing neurons in the upper segment of the SP zone. Cx45 was present on the cell bodies of human SP neurons, while Cx26 was found on both cell bodies and dendrites. Cx45, Cx36, and Cx26 were strongly expressed in the cortical plate, where newborn migrating neurons line up to form cortical layers. New information about the expression of 3 "neuronal" Cx isoforms in each cortical layer/zone (e.g., SP, cortical plate) and pharmacological data with cadmium and lanthanum may improve our understanding of the cellular mechanisms underlying neuronal development in human fetuses and potential vulnerabilities.

Quantitative In vivo MRI Assessment of Structural Asymmetries and Sexual Dimorphism of Transient Fetal Compartments in the Human Brain.

Structural asymmetries and sexual dimorphism of the human cerebral cortex have been identified in newborns, infants, children, adolescents, and adults. Some of these findings were linked with cognitive and neuropsychiatric disorders, which have roots in altered prenatal brain development. However, little is known about structural asymmetries or sexual dimorphism of transient fetal compartments that arise in utero. Thus, we aimed to identify structural asymmetries and sexual dimorphism in the volume of transient fetal compartments (cortical plate [CP] and subplate [SP]) across 22 regions. For this purpose, we used in vivo structural T2-weighted MRIs of 42 healthy fetuses (16.43-36.86 gestational weeks old, 15 females). We found significant leftward asymmetry in the volume of the CP and SP in the inferior frontal gyrus. The orbitofrontal cortex showed significant rightward asymmetry in the volume of CP merged with SP. Males had significantly larger volumes in regions belonging to limbic, occipital, and frontal lobes, which were driven by a significantly larger SP. Lastly, we did not observe sexual dimorphism in the growth trajectories of the CP or SP. In conclusion, these results support the hypothesis that structural asymmetries and sexual dimorphism in relative volumes of cortical regions are present during prenatal brain development.

Alveolar cortical plate changes associated with incisor retraction and its influence on the limits of orthodontic tooth movement.

OBJECTIVE: The extent to which the modelling behaviour of the anterior alveolus limits tooth movement remains unclear. Will the labial and lingual cortical plates model as incisors retract, or will they remain unchanged, therefore limiting the extent of possible tooth movement? SETTING AND SAMPLE POPULATION: Pre- and post-treatment lateral cephalometric radiographs of 29 bimaxillary protrusive patients of South Korean descent were examined. Treatment consisted of two premolar extractions in one or both arches with en masse retraction of the incisors using miniscrew anchorage. MATERIALS AND METHODS: Pre- and post-treatment measurements of both tooth and cortical plate position were made at various increments along the length of the root and then compared using paired t tests. RESULTS: Despite the use of miniscrew anchorage, the incisors were retracted by controlled tipping. The labial cortical plates in both arches modelled to follow tooth movement. Following retraction of the incisors in the maxilla, the incisor root approached the lingual cortical plate, which remained unchanged. In the mandible, the lingual cortical plate position was unchanged except at the level closest to the cementoenamel junction. CONCLUSIONS: The maxillary and mandibular lingual cortical plates did not model to follow the incisor movement while the labial cortical plates did. These findings suggest that lingual cortical plates may act as limitations to planned orthodontic tooth movement.

Evaluation of facial and palatal alveolar bone thickness and sagittal root position of maxillary anterior teeth on cone beam computerized tomograms.

BACKGROUND: Amount of bone covering the facial and palatal surface of the root and the sagittal root position are important parameters while considering an immediate implant placement. AIMS: This study measures the distance from cement-enamel junction (CEJ) to alveolar crest and thickness of alveolar bone of maxillary anterior teeth facially and palatally at 5 different points. MATERIALS AND METHODS: CBCT scans of 79 systemically healthy patients were evaluated by two calibrated and independent examiners. Measurements like: 1) distance from CEJ to Crest. 2) Thickness of facial and palatal alveolar bone at five different points a) Crest, b) 2 mm from the crest, c) mid root level, d) apical 3rd, e) apex. 3) Sagittal root position. 4) Labiopalatal distance at the apex. 5) Length of the bone from apex to the nasal floor for incisors. 6) Presence of fenestrations and dehiscences were assessed. RESULTS: Healthy maxillary anteriors were evaluated and less than 2 mm bone was seen at all five points, 0.5 to 1 mm bone is seen in all anteriors at crest, 2 mm from crest, midroot, apical 3rd level. 1 to 2 mm is seen at apex. Labiopalatal width at apex ranged from 3 mm to 13 mm with a mean of 7.45 ± 2.24 mm for centrals, 7.69 ± 2.14 mm for lateral incisors, and 6.76 ± 2.42 mm for canines. CONCLUSION: The present study supports the finding of very thin facial bone over maxillary anteriors and frequent occurrence of fenestrations and dehiscences. Pre-treatment evaluation of alveolar bone surrounding the maxillary anteriors is important to avoid complications during implant placement.

Functional Differentiation of Cholecystokinin-Containing Interneurons Destined for the Cerebral Cortex.

Although extensively studied postnatally, the functional differentiation of cholecystokinin (CCK)-containing interneurons en route towards the cerebral cortex during fetal development is incompletely understood. Here, we used CCKBAC/DsRed mice encoding a CCK promoter-driven red fluorescent protein to analyze the temporal dynamics of DsRed expression, neuronal identity, and positioning through high-resolution developmental neuroanatomy. Additionally, we developed a dual reporter mouse line (CCKBAC/DsRed::GAD67gfp/+) to differentiate CCK-containing interneurons from DsRed+ principal cells during prenatal development. We show that DsRed is upregulated in interneurons once they exit their proliferative niche in the ganglionic eminence and remains stably expressed throughout their long-distance migration towards the cerebrum, particularly in the hippocampus. DsRed+ interneurons, including a cohort coexpressing calretinin, accumulated at the palliosubpallial boundary by embryonic day 12.5. Pioneer DsRed+ interneurons already reached deep hippocampal layers by embryonic day 14.5 and were morphologically differentiated by birth. Furthermore, we probed migrating interneurons entering and traversing the cortical plate, as well as stationary cells in the hippocampus by patch-clamp electrophysiology to show the first signs of Na+ and K+ channel activity by embryonic day 12.5 and reliable adult-like excitability by embryonic day 18.5. Cumulatively, this study defines key positional, molecular, and biophysical properties of CCK+ interneurons in the prenatal brain.

Developmental Switch in Spike Timing-Dependent Plasticity and Cannabinoid-Dependent Reorganization of the Thalamocortical Projection in the Barrel Cortex.

UNLABELLED: The formation and refinement of thalamocortical axons (TCAs) is an activity-dependent process (Katz and Shatz, 1996), but its mechanism and nature of activity are elusive. We studied the role of spike timing-dependent plasticity (STDP) in TCA formation and refinement in mice. At birth (postnatal day 0, P0), TCAs invade the cortical plate, from which layers 4 (L4) and L2/3 differentiate at P3-P4. A portion of TCAs transiently reach toward the pia surface around P2-P4 (Senft and Woolsey, 1991; Rebsam et al., 2002) but are eventually confined below the border between L2/3 and L4. We previously showed that L4-L2/3 synapses exhibit STDP with only potentiation (timing-dependent long-term potentiation [t-LTP]) during synapse formation, then switch to a Hebbian form of STDP. Here we show that TCA-cortical plate synapses exhibit robust t-LTP in neonates, whose magnitude decreased gradually after P4-P5. After L2/3 is differentiated, TCA-L2/3 gradually switched to STDP with only depression (t-LTD) after P7-P8, whereas TCA-L4 lost STDP. t-LTP was dependent on NMDA receptor and PKA, whereas t-LTD was mediated by Type 1 cannabinoid receptors (CB1Rs) probably located at TCA terminals, revealed by global and cortical excitatory cell-specific knock-out of CB1R. Moreover, we found that administration of CB1R agonists, including Δ(9)-tetrahydrocannabinol, caused substantial retraction of TCAs. Consistent with this, individual thalamocortical axons exuberantly innervated L2/3 at P12 in CB1R knock-outs, indicating that endogenous cannabinoid signaling shapes TCA projection. These results suggest that the developmental switch in STDP and associated appearance of CB1R play important roles in the formation and refinement of TCAs. SIGNIFICANCE STATEMENT: It has been shown that neural activity is required for initial synapse formation of thalamocortical axons with cortical cells, but precisely what sort of activities in presynaptic and postsynaptic cells are required is not yet clear. In addition, how activity is further translated into structural changes is unclear. We show here that the period during which spike timing-dependent long-term potentiation and depression (t-LTP, t-LTD) can be induced closely matches the time course of synapse formation and retraction, respectively, at the thalamocortical synapse. Moreover, administration of cannabinoid agonists, which mimic t-LTD, caused TCA retraction, suggesting that cannabinoids translate physiological changes into morphological consequences.

Quantitative comparison of cerebral artery development in human embryos with other eutherians.

The embryonic and early fetal human brain is known to undergo extraordinary expansion of its cellular population during embryonic and early fetal life, and is critically dependant on a steady supply of nutrients and oxygen for proper brain development. Quantitative analysis of the internal radius of the aorta and cerebral arteries in a range of eutherian mammals has been used to compare arterial flow to the developing human brain with that to the brains of non-human eutherians. Human embryos showed a much steeper rise of internal radius of the aorta with increasing body size than the embryos of non-human eutherians, but the thickness of the aorta rose at the same pace relative to body size in both humans and non-humans, suggesting that aortic pressure is similar in all eutherian embryos of a similar size. The sums of internal radii of both the internal carotids and vertebral arteries of human embryos raised to the fourth power were much lower at embryonic stages (less than 22 mm body length) than in non-human eutherians, were similar between humans and non-humans at 22-30 mm body length, and exceeded the non-humans at body lengths of more than 30 mm. The relative size of the internal calibre of the cerebral feeder arteries (internal carotid and vertebral) to the aorta did not change between embryonic and fetal sizes in either humans or non-humans. The findings suggest that the developing human brain may actually receive less blood flow at embryonic sizes (less than 22 mm body length) than do other mammalian embryos of a similar body size, but that internal carotid and vertebral flow is higher in human fetuses (body length greater than 30 mm) than in developing non-humans of the same body size. Increased flow to the developing human brain relative to non-humans is achieved by simultaneous increases in both aortic and cerebral feeder artery internal calibre.

Influence of the maxillary third molars and the surrounding cortical plate during maxillary tooth movement with TADS- A CBCT Study.

OBJECTIVE: To determine the influence of the presence/absence of third molars and intact/loss of cortical plate of the maxillary tuberosity on the amount of distal movement of the maxillary first permanent molar during distal movement of the maxillary dentition with mini-implants. MATERIALS AND METHODS: Thirty six maxillary tuberosity sites were evaluated in eighteen young adult patients. The distal movement of the entire maxillary dentition was performed with mini-implants with 200 g of distalising force applied from the mini-implant placed in the maxillary posterior buccal region to attachments placed on the arch wire between the maxillary lateral incisor and canine bilaterally. The distal movement of the maxillary first permanent molars was measured on lateral cephalograms. The maxillary tuberosity sites with intact cortical plate due to congenitally missing third molars or atraumatic extraction of third molars (G1), partial loss of cortical plate due to surgical removal of third molars (G2), fully erupted third molars (G4), third molars located at (G3), and below the cementoenamel junction (G5) were evaluated with cone beam computed tomography. One way Anova and Fisher LSD test was done. RESULTS: The order of greater to lesser amount of distal movement of the maxillary first permanent molar depending on the integrity of maxillary of tuberosity was partial loss of cortical plate, third molars at the cementoenamel junction, third molars below the cementoenamel junction, intact cortical plate and fully erupted third molars. CONCLUSION: The integrity of the cortical plate and the relative position of the maxillary third molar to the second molar influence the amount of distal movement of the maxillary first permanent molar during distal movement of the maxillary teeth with TADS. CLINICAL RELEVANCE: The amount of distal movement of the maxillary dentition appears to depend on the presence or absence of the third molars and the condition of the cortical plate in the region of the maxillary tuberosity and thereby greatly influence the outcome of treatment.

Combined distalization and lingual cortex remodeling during mandibular growth for facial profile improvement: a case report.

Borderline crowding poses a challenge in deciding whether or not to prescribe premolar extraction. This case report describes the two-phase nonextraction orthodontic treatment of an 11-year-old girl with a hyperdivergent skeletal Class I pattern exhibiting anterior crowding and moderate lip protrusion. The initial phase of treatment included maxillary and mandibular expansion to correct the transverse discrepancy as an early intervention. Subsequently, comprehensive treatment was initiated at the age of 13 years, with fully erupted permanent second molars and growth potential remaining. Phase II treatment involved a second round of maxillary expansion, followed by simultaneous bimaxillary total arch intrusive distalization, using interradicular, temporary skeletal anchorage devices to correct dental crowding and improve the facial profile. Although the limited retromolar space posed a challenge to mandibular tooth distalization, gradual bone remodeling was observed in the lingual cortex of the mandibular body, enabling sufficient orthodontic tooth movement without noticeable side effects. After 4 years 3 months of treatment, her dental crowding was relieved, with significant improvement in the facial profile and proper occlusion. The treatment outcomes remained stable 2 years 4 months after retention.

X-ray and anatomical features of the lower jaw alveolar cortical layer in children.

INTRODUCTION: the world studies showed the interest in measurement of the buccal or anterior cortical plate thickness. Data indicate a significant superiority of the spongy substance over the compact one in the distal part of the jaw, which makes it possible to think about a higher effectiveness of transcortical injections. The empirical "rule of 10″ provides for the choice of a method of anesthesia in children for primary teeth but demonstrates difficulties with high-quality anesthesia accompanied for permanent teeth. Therefore, the importance of clinical examination and anatomical investigation of the jaw cortical plate in children for competent planning of transcortical interventions has been determined. AIM: To study the features of the clinical and X-ray anatomy of the cortical layer in distal alveolar part of the mandible in children. MATERIAL AND METHODS: The assessment of the X-ray anatomical characteristics of the mandible was carried out according to 150 anonymized cone-beam computed tomograms of patients aged 6-12 years, performed for the treatment of major diseases. Qualitative assessment and examination of the cortical plate of the distal alveolar part of the mandible were carried out on the skeletonized certified preparations of aged 6-12 in the amount of 50. RESULTS: The age characteristics of the cortical plate in the area of the chewing group of teeth in the mandible were determined according to macro anatomical studies, which confirms with the X-ray results. Therefore, the obtained images serve as actual confirmation of X-ray studies, which are ranked by age. The thickness of the cortical plate in the second primary molar of the mandible in subgroups 6, 7 and 8 years has a proportional increase from the cervical region to the apical projection. The average thickness of the cortical plate is 1.57 mm at 6 years, 1.52 mm at 7 years, 1.6 mm at 8 years and 1.84 at 9 years. The cortical plate thickness in the first primary molar of the mandible in subgroups 6 and 7 years has a proportional decrease from the cervical region to the apical projection as well as an inverse proportion to age. The average thickness of the cortical plate is 1.33 mm. In the first molar of the mandible at the age limit of 6-12 years the attention is drawn to the linear increase in tissue volume from the cervical region to the apical projection up to 8 years. At 6-8 years the average thickness of the cortical plate in this age group is 1.74 ± 0.2 mm, at 9 years - 2.03 mm, at 10 - average value in the cervical region it is 1.53 ± 0.23 mm, in the root middle it is 2.19 ± 0.13 mm and in the apical projection it is 1.98 ± 0.16 mm, at 11-2.22 mm and at 12-2.35 mm. For the second primary molar the average thickness of the buccal cortical plate of the second primary molar is 1.4 mm in cervical part, 1.68 mm in the root middle and 1.81 mm in the apical projection. Finally, thickness of the buccal cortical plate in the cervical region of the first permanent molar is 2 mm in groups. CONCLUSION: The study makes it possible to determinate with noninvasive way the age limit for the least pronounced zone of the buccal cortical plate.

Telencephalon Organoids Derived from an Individual with ADHD Show Altered Neurodevelopment of Early Cortical Layer Structure.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that occurs in early childhood and can persist to adulthood. It can affect many aspects of a patient's daily life, so it is necessary to explore the mechanism and pathological alterations. For this purpose, we applied induced pluripotent stem cell (iPSC)-derived telencephalon organoids to recapitulate the alterations occurring in the early cerebral cortex of ADHD patients. We found that telencephalon organoids of ADHD showed less growth of layer structures than control-derived organoids. On day 35 of differentiation, the thinner cortex layer structures of ADHD-derived organoids contained more neurons than those of control-derived organoids. Furthermore, ADHD-derived organoids showed a decrease in cell proliferation during development from day 35 to 56. On day 56 of differentiation, there was a significant difference in the proportion of symmetric and asymmetric cell division between the ADHD and control groups. In addition, we observed increased cell apoptosis in ADHD during early development. These results show alterations in the characteristics of neural stem cells and the formation of layer structures, which might indicate key roles in the pathogenesis of ADHD. Our organoids exhibit the cortical developmental alterations observed in neuroimaging studies, providing an experimental foundation for understanding the pathological mechanisms of ADHD.

Autotransplantation of Maxillary Third Molar with Its Attached Buccal Cortical Plate Combined with a Connective Tissue Graft.

INTRODUCTION: Tooth replacement often leads to insufficient vertical volume in the recipient socket bone. The aim of this novel report is to present a successful fully guided autotransplantation of a maxillary right third molar (tooth #1) with its attached buccal plate. The procedure was combined with a palatal connective tissue graft to reconstruct a buccal hard and soft tissue defect of an irreparable maxillary right first molar (tooth #3). METHODS: A 45-year-old man complaining of pain in tooth #3 came to the clinic. Tooth #3 was non-restorable due to an extensive caries and a vertical root fracture of the mesiobuccal root, leading to a total loss of the buccal cortical plate. Guided autotransplantation of tooth #1 was completed by using 3-dimensional surgical templates for implant burs and a 3-dimensional-printed replica. After positioning the donor tooth, the cortical plate was fixed to the recipient socket with osteosynthesis screws. A connective tissue graft was also harvested to increase the band of keratinized gingiva and the thickness of the buccal soft tissue. At 6-month follow-up, the screws were removed, showing excellent regeneration throughout the buccal area. RESULTS: At 3-year follow-up, the transplanted tooth was asymptomatic, with a natural bone level and no signs of replacement or inflammatory root resorption. CONCLUSIONS: The use of a donor tooth and its attached bone cortical plate combined simultaneously with a connective tissue graft appears to improve hard and soft tissues in a single procedure.

Proximity of maxillary molar apexes to the cortical bone surface and the maxillary sinus.

Objectives: This study aimed to analyze the proximity of maxillary molar roots to their overlying cortical bone surfaces and the maxillary sinus. Materials and Methods: Cone-beam computed tomographic images of 151 patients with completely erupted upper molars that had 3 separate roots were studied. The following distances were measured: from the root apex to the cortical plate and maxillary sinus floor, and from the apical 3-mm level of the root to the cortical plate. Differences between groups were analyzed with 1-way analysis of variance and the Scheffé post hoc test, the significance of differences between cone-beam computed tomography views with the paired t-test, and the significance of differences among age groups with linear regression analysis. The significance level was set at p < 0.05. Results: The mesiobuccal and distobuccal root apexes of maxillary second molars were more distant from the buccal cortical plate than the maxillary first molars (p < 0.05). The apical 3-mm level of the mesiobuccal root of the first molar was closer to the buccal cortical bone than the second molar (p < 0.05). In the maxillary first molars, the thickness of the buccal cortical bone decreased in all roots with age (p < 0.05). In all root apexes of both molars, the difference in the vertical level between the maxillary sinus floor and the root apex increased with age (p < 0.05). Conclusions: Awareness of the anatomical profile of maxillary molar apices in relation to the cortical bones and maxillary sinus will be beneficial for apical surgery.

Comparison Between the Bone Lid Technique and the Traditional Technique in Surgical Treatment of the Posterior Mandibular Lesions: A Randomized Controlled Trial.

Introduction Cystic lesions of the jaws and the impacted teeth are two of the most common cases that require surgical intervention in oral and maxillofacial surgery; however, surgeons also frequently use a traditional technique that involves the removal of the buccal bone plate. This study was conducted to compare the clinical and radiologic outcomes of the bone lid technique and the traditional technique. Methods This randomized controlled trial included 20 patients who were randomly divided into two groups (n = 10 each): the T group, in which the lesions were accessed using the traditional technique with classical rotating instruments, and the BL group, in which the lesions were accessed with the bone lid technique performed using a piezoelectric device, with repositioning of the buccal bone plate. Operative time, pain, edema, inferior alveolar nerve injury, and bone defect healing were measured during clinical and radiological follow-ups at 24 h, 72 h, one week, one month, and six months after the surgery. Results Normal soft tissue and bone healing were observed in all cases except one case in the BL group. The T group had a shorter mean operative time than the BL group. In terms of pain, edema, and inferior alveolar nerve injury, the groups did not differ statistically significantly. The percentage of bone defect healing was significantly greater in the BL group than in the T group after six months of follow-up. Conclusion The bone lid technique performed using a piezoelectric device was effective and safe for managing lesions in the posterior mandibular region and was not associated with increased postoperative complications. The disadvantages of this technique include a longer operative time and the need for fixation tools in some cases. In contrast, this technique outperforms the traditional technique in terms of reducing bone loss and improving the healing of bone defects.