Stress-induced oxytocin release and oxytocin cell number and size in prepubertal and adult male and female rats.

Studies indicate that adolescent exposure to stress is a potent environmental factor that contributes to psychological and physiological disorders, though the mechanisms that mediate these dysfunctions are not well understood. Periadolescent animals display greater stress-induced hypothalamic-pituitary-adrenal (HPA) axis responses than adults, which may contribute to these vulnerabilities. In addition to the HPA axis, the hypothalamo-neurohypophyseal tract (HNT) is also activated in response to stress. In adults, stress activates this system resulting in secretion of oxytocin from neurons in the supraoptic (SON) and paraventricular (PVN) nuclei. However, it is currently unknown whether a similar or different response occurs in prepubertal animals. Given the influence of these hormones on a variety of emotional behaviors and physiological systems known to change as an animal transitions into adulthood, we investigated stress-induced HPA and HNT hormonal responses before and after stress, as well as the number and size of oxytocin-containing cells in the SON and PVN of prepubertal (30d) and adult (70d) male and female rats. Though we found the well-established protracted adrenocorticotropic hormone and corticosterone response in prepubertal males and females, only adult males and prepubertal females showed a significant stress-induced increase in plasma oxytocin levels. Moreover, though we found no pubertal changes in the number of oxytocin cells, we did find a pubertal-related increase in oxytocin somal size in both the SON and PVN of males and females. Taken together, these data indicate that neuroendocrine systems can show different patterns of stress reactivity before and after adolescent development and that these responses can be further modified by sex. Given the impact of these hormones on a variety of systems, it will be imperative to further explore these changes in hormonal stress reactivity and their role in adolescent health.

Speckle-variance optical coherence tomography: a novel approach to skin cancer characterization using vascular patterns.

Non-invasive imaging devices are currently being utilized in research and clinical settings to help visualize, characterize, anddiagnose cancers of the skin. Speckle-variance optical coherence tomography (svOCT) is one such technology that offers considerable promise for non-invasive, real time detection of skin cancers given its added ability to show changes in microvasculature. We present four early lesions of the face namely sebaceous hyperplasia, basal cell skin cancer, pigmented actinic keratosis, and malignant melanoma in situ that each display different important identification markers on svOCT. Up until now, svOCT has mainly been evaluated for lesion diagnosis using transversal (vertical) sections. Our preliminary svOCT findings use dynamic en face (horizontal) visualization to differentiate lesions based on their specific vascular organizations. These observed patterns further elucidate the potential of this imaging device to become a powerful tool in patient disease assessment.

Artificial Intelligence for 3D Reconstruction from 2D Panoramic X-rays to Assess Maxillary Impacted Canines.

The objective of this study was to explore the feasibility of current 3D reconstruction in assessing the position of maxillary impacted canines from 2D panoramic X-rays. A dataset was created using pre-treatment CBCT data from a total of 123 patients, comprising 74 patients with impacted canines and 49 patients without impacted canines. From all 74 subjects, we generated a dataset containing paired 2D panoramic X-rays and pseudo-3D images. This pseudo-3D image contained information about the location of the impacted canine in the buccal/lingual, mesial/distal, and apical/coronal positions. These data were utilized to train a deep-learning reconstruction algorithm, a generative AI. The location of the crown of the maxillary impacted canine was determined based on the output of the algorithm. The reconstruction was evaluated using the structure similarity index measure (SSIM) as a metric to indicate the quality of the reconstruction. The prediction of the impacted canine's location was assessed in both the mesiodistal and buccolingual directions. The reconstruction algorithm predicts the position of the impacted canine in the buccal, middle, or lingual position with 41% accuracy, while the mesial and distal positions are predicted with 55% accuracy. The mean SSIM for the output is 0.71, with a range of 0.63 to 0.84. Our study represents the first application of AI reconstruction output for multidisciplinary care involving orthodontists, periodontists, and maxillofacial surgeons in diagnosing and treating maxillary impacted canines. Further development of deep-learning algorithms is necessary to enhance the robustness of dental reconstruction applications.

Assessment of malalignment factors related to the Invisalign treatment time aided by automated imaging processes.

OBJECTIVES: To identify predictors regarding the type and severity of malocclusion that affect total Invisalign treatment duration based on an intraoral digital scan. MATERIALS AND METHODS: The subjects of this retrospective clinical cohort were 116 patients treated with Invisalign. A deep learning method was used for automated tooth segmentation and landmark identification of the initial and final digital models. The changes in the six degrees of freedom (DOF), representing types of malalignment, were measured. Linear regression was performed to find the contributing factors associated with treatment time. In addition, the Peer Assessment Rating (PAR) score and a composite score combining 6 DOF were correlated separately to the treatment time. RESULTS: The number of trays differed between sexes (P = .0015). The absolute maximum torque was marginally associated with the total number of trays (P = .0518), while the rest of the orthodontic tooth movement showed no correlation. The composite score showed a higher correlation with the total number of trays (P = .0045) than did individual tooth movement. Pretreatment upper and lower anterior segment PAR scores were positively associated with the treatment time (P < .001). CONCLUSIONS: There is not enough evidence to conclude that certain types of tooth movement affect the total aligner treatment time. A composite score seems to be a better predictor for total treatment time than do individual malalignment factors in aligner treatment. Upper and lower anterior malalignment factors have a significant effect on the treatment duration.

In situ tissue engineering of the tendon-to-bone interface by endogenous stem/progenitor cells.

The long-term success of surgical repair of rotator cuff tears is largely dependent on restoration of a functional tendon-to-bone interface. We implemented micro-precise spatiotemporal delivery of growth factors in three-dimensional printed scaffolds for integrative regeneration of a fibrocartilaginous tendon-to-bone interface. Sustained and spatially controlled release of tenogenic, chondrogenic and osteogenic growth factors was achieved using microsphere-based delivery carriers embedded in thin membrane-like scaffolds. In vitro, the scaffolds embedded with spatiotemporal delivery of growth factors successfully guided regional differentiation of mesenchymal progenitor cells, forming multiphase tissues with tendon-like, cartilage-like and bone-like regions. In vivo, when implanted at the interface between the supraspinatus tendon and the humeral head in a rat rotator cuff repair model, these scaffolds promoted recruitment of endogenous tendon progenitor cells followed by integrative healing of tendon and bone via re-formation of strong fibrocartilaginous interfaces. Our findings demonstrate the potential of in situ tissue engineering of tendon-to-bone interfaces by endogenous progenitor cells. The in situ tissue engineering approach shows translational potential for improving outcomes after rotator cuff repair.

A Combination of Oxo-M and 4-PPBP as a potential regenerative therapeutics for tendon injury.

Tendons injuries frequently result in scar-like tissue with poor biochemical structure and mechanical properties. We have recently reported that CD146+ perivascular originated tendon stem/progenitor cells (TSCs), playing critical roles in tendon healing. Here, we identified highly efficient small molecules that selectively activate endogenous TSCs for tendon regeneration. Methods: From a pool of ERK1/2 and FAK agonists, Oxo-M and 4-PPBP were identified, and their roles in tenogenic differentiation of TSCs and in vivo tendon healing were investigated. Controlled delivery of Oxo-M and 4-PPBP was applied via PLGA µS. Signaling studies were conducted to determine the mechanism for specificity of Oxo-M and 4-PPBP to CD146+ TSCs. Results: A combination of Oxo-M and 4-PPBP synergistically increased the expressions of tendon-related gene markers in TSCs. In vivo, delivery of Oxo-M and 4-PPBP significantly enhanced healing of fully transected rat patellar tendons (PT), with functional restoration and reorganization of collagen fibrous structure. Our signaling study suggested that Oxo-M and 4-PPBP specifically targets CD146+ TSCs via non-neuronal muscarinic acetylcholine receptors (AChR) and σ1 receptor (σ1) signaling. Principal conclusions: Our findings demonstrate a significant potential of Oxo-M and 4-PPBP as a regenerative therapeutics for tendon injuries.

Noninvasive Long-term Monitoring of Actinic Keratosis and Field Cancerization Following Treatment with Ingenol Mebutate Gel 0.015.

OBJECTIVE: To determine whether actinic keratosis and photodamaged perilesional areas (field cancerization) treated successfully with topical ingenol mebutate gel 0.015% remained clear one year later, and to treat actinic keratosis and perilesional skin not treated one year earlier. DESIGN: Single-center, single-arm, open-label extension of an original clinical study completed one year earlier. SETTING: An outpatient clinic. PARTICIPANTS: Fifteen of the original 28 study patients enrolled in and who completed the extension phase. MEASUREMENTS: All treated and untreated lesions in the original study were evaluated clinically, dermoscopically, and with optical coherence tomography at Day 0 of the extension study. Previously untreated lesions were then treated with ingenol mebutate gel 0.015% for three days and reevaluated at Day 60. RESULTS: There was no significant increase in actinic keratoses over one year. The majority of actinic keratoses not treated in the original study were still present at the beginning of the extension study. Following treatment, 69 percent of these lesions cleared by Day 60 of the extension study, which was not significantly different from the 79 percent clearance observed in the original study. CONCLUSION: Ingenol mebutate 0.015% maintained clearance of lesions treated one year earlier. Optical coherence therapy demonstrated its reliability as a noninvasive mode of diagnosis for actinic keratosis as well as actinic damage in the surrounding areas of field cancerization. Optical coherence therapy also showed that previously untreated lesions exhibited similar clearance rates once treated with the medication.

Pubertal shifts in adrenal responsiveness to stress and adrenocorticotropic hormone in male rats.

Studies have indicated significant pubertal-related differences in hormonal stress reactivity. We report here that prepubertal (30 days) male rats display a more protracted stress-induced corticosterone response than adults (70 days), despite showing relatively similar levels of adrenocorticotropic hormone (ACTH). Additionally, we show that adrenal expression of the ACTH receptor, melanocortin 2 receptor (Mc2r), is higher in prepubertal compared to adult animals, and that expression of melanocortin receptor accessory protein (Mrap), a molecule that chaperones MC2R to the cell surface, is greater in prepubertal males following stress. Given that these data suggest a pubertal shift in adrenal sensitivity to ACTH, we directly tested this possibility by injecting prepubertal and adult males with 6.25 or 9.375µg/kg of exogenous rat ACTH and measured their hormone levels 30 and 60min post-injection. As these doses resulted in different circulating levels of ACTH at these two ages, we performed regression analyses to assess the relationship between circulating ACTH and corticosterone concentrations. We found no difference between the ages in the correlation between ACTH and corticosterone levels at the 30min time point. However, 60min following the ACTH injection, we found prepubertal rats had significantly higher corticosterone concentrations at lower levels of ACTH compared to adults. These data suggest that prolonged exposure to ACTH leads to greater corticosterone responsiveness prior to puberty, and indicate that changes in adrenal sensitivity to ACTH may, in part, contribute to the protracted hormonal stress response in prepubertal rats.