Assessment of Medical Clowning in Influencing the Anxiety and Behavior Scores of Children Undergoing Various Dental Treatments and the Stress Levels of the Operator.

Aim: To investigate the potential effectiveness of "medical clowns" on preoperative, intraoperative, and postoperative anxiety of children undergoing various dental treatments and also its effect on the operator's stress levels in a dental setup. Materials and methods: A total of 170 pediatric patients, aged 4-8 years, indicated for preventive therapy, extractions, restorative, and endodontics were included and divided into two groups [group I-audiovisual (A-V) aids; group II-medical clowns], group of 85 patients each after recording Modified yale preoperative scale. Both pre- and postoperatively, Frankl's behavior score was recorded for each patient. During treatment, the face, legs, activity, cry, consolability (FLACC) pain scale, and dental operator's stress level were recorded. Results: Intervention of medical clowns positively influenced children during dental treatment by increasing their pain threshold. The majority of children showed positive Frankl rating scales after dental treatment. Also, the operator's stress was significantly reduced, which led to enhanced treatment outcomes. Conclusion: Humor yields the power of healing, distracts pediatric patients, reduces their anxiety, and alleviates their pain, conferring the patients with a sense of laughter, creativity, and care.Therefore, medical clowns in pediatric dentistry can prove to be serviceable and valuable as a nonpharmacological approach to behavior management. How to cite this article: Aggarwal P, Mathur S, Chopra R. Assessment of Medical Clowning in Influencing the Anxiety and Behavior Scores of Children Undergoing Various Dental Treatments and the Stress Levels of the Operator. Int J Clin Pediatr Dent 2024;17(1):59-66.

Smartphones' impact on nursing performances: a cross-sectional multicenter study.

Background: In recent years, the technology world has significantly shaped society. This study aims to survey the views of registered nurses with hospital working experience regarding the personal communication devices use impact in hospital units. The secondary outcome of this study was to identify differences in mobile device use based on demographic and organizational factors. Study design: Cross-sectional study by survey. Methods: The questionnaire comprises 22 items divided into four sections. Overall 778 questionnaires were included in the study, 329 questionnaires were collected on pen-and-paper, whereas 449 by an online survey. Results: Findings showed that smartphones have a different impact on performance, utilization and impact scale according to gender, age and educational attainment. Generally males using more frequently personal communication devices for non-workrelated activities affected negatively their working performance by respect to females. Moreover, younger nurses report being more distracted by using smartphones for non-work-related activities than older nurses. At the same time, younger nurses believe that smartphones may lead to an improvement in patient care skills. Nurses with fewer years of service (1 month - 10 years) report being more distracted by non-work-related activities on their smartphones than nurses with more years of service (>20 years). Conclusions: The smartphone is a potential distraction source. The most exposed groups are the younger nurses' and those with little work experience, and both groups (young age, less experience) can be considered factors for potential distraction.

Evaluating the Readability of Patient Education Materials for Anterior Vertebral Body Tethering, Distraction-Based Methods, and Posterior Spinal Fusion for the Treatment of Pediatric Spinal Deformity.

BACKGROUND: The Internet is an important source of information for patients, but its effectiveness relies on the readability of its content. Patient education materials (PEMs) should be written at or below a sixth-grade reading level as outlined by agencies such as the American Medical Association. This study assessed PEMs' readability for the novel anterior vertebral body tethering (AVBT), distraction-based methods, and posterior spinal fusion (PSF) in treating pediatric spinal deformity. METHODS: An online search identified PEMs using the terms "anterior vertebral body tethering," "growing rods scoliosis," and "posterior spinal fusion pediatric scoliosis." We selected the first 20 general medical websites (GMWs) and 10 academic health institution websites (AHIWs) discussing each treatment (90 websites total). Readability tests for each webpage were conducted using Readability Studio software. Reading grade levels (RGLs), which correspond to the US grade at which one is expected to comprehend the text, were calculated for sources and independent t tests compared with RGLs between treatment types. RESULTS: The mean RGL was 12.1 ± 2.0. No articles were below a sixth-grade reading level, with only 2.2% at the sixth-grade reading level. AVBT articles had a higher RGL than distraction-based methods (12.7 ± 1.6 vs 11.9 ± 1.9, P = 0.082) and PSF (12.7 ± 1.6 vs 11.6 ± 2.3, P = 0.032). Materials for distraction-based methods and PSF were comparable (11.9 ± 1.9 vs 11.6 ± 2.3, P = 0.566). Among GMWs, AVBT materials had a higher RGL than distraction-based methods (12.9 ± 1.4 vs 12.1 ± 1.8, P = 0.133) and PSF (12.9 ± 1.4 vs 11.4 ± 2.4, P = 0.016). CLINICAL RELEVANCE: Patients' health literacy is important for shared decision-making. Assessing the readability of scoliosis treatment PEMs guides physicians when sharing resources and discussing treatment with patients. CONCLUSION: Both GMWs and AHIWs exceed recommended RGLs, which may limit patient and parent understanding. Within GMWs, AVBT materials are written at a higher RGL than other treatments, which may hinder informed decision-making and patient outcomes. Efforts should be made to create online resources at the appropriate RGL. At the very least, patients and parents may be directed toward AHIWs; RGLs are more consistent.

Comparison of Effectiveness of Audio and VR Distraction Techniques in Managing Pediatric Dental Patients.

Aim: In order to manage pediatric dental patients, this study set out to assess the effectiveness of two distraction techniques: audio and virtual reality (VR) with tell, show, and do technique (TSD). Materials and Methods: Forty-five children aged 6-10 years were selected for the present randomized control trial. They were split into three groups at random. Group 1 control group: tell-show-do, Group 2: audio distraction, and Group 3: VR distraction. Both pretreatment and postoperative anxiety levels were measured by modified Venham's anxiety rating scale (MVARS). Results: In each of the three groups, there was a statistically significant difference between the child's pre- and post-treatment anxiety levels. VR distraction group experienced the greatest reduction in anxiety. Conclusion: All three methods were similarly successful at lowering anxiety while virtual reality distraction outperformed compared to other techniques.

Virtual Reality Distraction: A Novel Behaviour Management Technique.

Virtual reality distraction (VRD) is developing technologies for behavior management that can assist a child in adjusting to the dental setting and provide high-quality dental care. The purpose of this literature is to shed light on VRD and its application to the treatment of pediatric dental patients.

Retrospective analysis of urethral anastomosis with ancillary maneuvers and intraoperative biaxial defect measurements to achieve a tension free guidance system for redo PFUDD treatment.

OBJECTIVES: Redo surgery for pelvic fracture urethral distraction defects (PFUDDs) is still a challenge. the long urethral defect makes it difficult while the high tension increase the recurrence rate. Although certain ancillary maneuvers can relieve tension, there is no consensus or guidelines for the prediction/planning of the selection. In this study, we present our experience with developing an intraoperative guidance system to achieve tension-free urethral anastomosis. PATIENTS AND METHODS: A total of 91 recurrent PFUDD patients managed at our center between 2020 and 2022 were retrospectively analyzed. The patients underwent scar removing and urethral anastomosis. For the long defect and high-tension cases, 6 kinds of tension-relieving maneuvers were used respectively during the process of urethral anastomosis. Preoperative assessment of the urethrogram was done before surgery, while biaxial (vertical and horizontal) defect measurements were performed intraoperatively. The patients were followed-up for 12 months (8.9 ± 4.2), furthermore, recurrence and complications were analyzed. RESULTS: The overall success rate was 86.81%. The mean defect in urethrogram was 2.9 ± 1.1 cm. 27 simple anastomosis was performed when the vertical plus horizontal defect was less than 2 cm with 11.11% recurrence. 24 cavernous septum splittings were performed when the horizontal defect was greater than 2 cm with 8.33% recurrence. 21 inferior pubectomies were performed when the horizontal defect was greater than 3 cm with 19.05% recurrence. 15 ancillary distal urethra manipulations (fully distal urethral mobilization, urethral suspension and corpus cavernosa folding) were performed when the vertical defect was 3 to 4 cm with 13.33 recurrence. 4 reroutings were performed when the vertical defect was greater than 4 cm with 25.00% recurrence. CONCLUSIONS: Ancillary maneuvers are effective for reducing tension in redo urethral anastomosis. Measurement of divergent vertical and horizontal urethral defects could guide the selection of ancillary maneuvers. Combined tension-relieving maneuvers is recommended according to the defect direction and length to achieve a tension-free anastomosis.

Comparing Ruminative and Distracting Responses and Emotion Regulation Difficulties in Early Community Adolescents With and Without Self-Harm.

Objectives: This study aimed to compare the demographic characteristics, responses to negative emotions, and difficulties in emotion regulation between self-harming adolescents and control individuals aged 12-14 years from the community. Methods: Data were collected from adolescents in Chungcheong Province, South Korea, between September 2021 and November 2022. Demographic characteristics and responses to the Depressed Mood Questionnaire and Difficulties in Emotion Regulation Scale-16 (DERS-16) were compared between the self-harm and control groups. Results: The self-harm group exhibited a higher prevalence of child abuse (odds ratio [OR]=4.787, 95% confidence interval [CI]=1.591-14.409, p=0.005) and school bullying victimization (OR=4.495, 95% CI=2.353-8.588, p<0.001) than those in the control group. The selfharm group displayed higher levels of rumination (t=7.88, p<0.001) and reduced distraction responses (reverse score t=2.25, p=0.025) than those of the control group. Additionally, the self-harm group scored higher on all subscales and the total DERS-16 score (t=7.61, p<0.001). Conclusion: Interventions for self-harming adolescents should address child abuse and bullying victimization. Prevention programs for self-harming adolescents should focus on reducing rumination responses, increasing distractive responses, and addressing difficulties in emotion regulation using dialectical behavior therapy-skill training.

Virtual Reality Distraction for Needle-Related Pain and Distress in Children: A Multicenter Randomized Controlled Trial.

This international multicenter randomized controlled trial aimed to compare the effectiveness of virtual reality (VR) distraction with an identical non-VR game in reducing needle-related pain and anxiety in children undergoing venous blood draw. The study involved 304 children aged 5-9 years undergoing a blood draw procedure, randomly allocated to one of three groups: VR distraction, non-VR distraction, and control group (usual care). The distraction task was based on the Multiple Object Tracking (MOT) paradigm, and the game was identical in design and gameplay for both VR and non-VR distraction groups. The primary outcome was self-reported pain intensity using the Faces Pain Scale-Revised (FPS-R). Secondary outcomes included child distress, attention/distraction to the blood draw, and parent and medical staff satisfaction with procedure. Analyses were conducted using analysis of variance and multivariable linear regression models. The results showed that VR distraction and non-VR distraction performed similarly, showing large effect sizes compared with standard care. There was no significant difference between the two types of distraction. The study's findings suggest that VR and non-VR distraction are similarly effective in reducing needle-related pain and anxiety in children undergoing venous blood draw. This is the first well-powered study comparing modern VR distraction with an identical task displayed on a smartphone or monitor screen. The study's results have important implications for using VR in clinical settings and suggest that investing in expensive VR equipment for acute pain management may not be necessary. The study protocol was pre-registered on Open Science Framework at https://osf.io/frsyc.

Novel patient-specific helical maxillary distractor: an in vitro feasibility study.

At present, stock linear distractors are used for internal maxillary distraction osteogenesis. However, the authors' research group has demonstrated, through an in silico analysis, that linear distraction leads to bone deformities and malocclusion, whereas helical distraction can yield ideal outcomes. A system for designing and manufacturing custom helical distractors has recently been developed, and the feasibility of these appliances now needs to be assessed. This study was, therefore, conducted to gain an initial insight into their feasibility. The study had two goals. First, it aimed to demonstrate, in an in vitro model, that the novel system of custom helical distraction can produce appropriate clinical outcomes. The second aim was to compare the performance of custom helical distractors with that of stock devices and hybrid devices (i.e., linear appliances that feature patient-specific footplates). Interpreting the results as trends, this study showed that the system of custom helical distraction resulted in in vitro outcomes that were superior to those obtained with stock and hybrid devices.

Resolving uncertainty on the fly: modeling adaptive driving behavior as active inference.

Understanding adaptive human driving behavior, in particular how drivers manage uncertainty, is of key importance for developing simulated human driver models that can be used in the evaluation and development of autonomous vehicles. However, existing traffic psychology models of adaptive driving behavior either lack computational rigor or only address specific scenarios and/or behavioral phenomena. While models developed in the fields of machine learning and robotics can effectively learn adaptive driving behavior from data, due to their black box nature, they offer little or no explanation of the mechanisms underlying the adaptive behavior. Thus, generalizable, interpretable, computational models of adaptive human driving behavior are still rare. This paper proposes such a model based on active inference, a behavioral modeling framework originating in computational neuroscience. The model offers a principled solution to how humans trade progress against caution through policy selection based on the single mandate to minimize expected free energy. This casts goal-seeking and information-seeking (uncertainty-resolving) behavior under a single objective function, allowing the model to seamlessly resolve uncertainty as a means to obtain its goals. We apply the model in two apparently disparate driving scenarios that require managing uncertainty, (1) driving past an occluding object and (2) visual time-sharing between driving and a secondary task, and show how human-like adaptive driving behavior emerges from the single principle of expected free energy minimization.

Complications of Surgically Assisted Rapid Maxillary/Palatal Expansion (SARME/SARPE)-A Retrospective Analysis of 185 Cases Treated at a Single Center.

Objectives: The study aims to assess and classify complications in patients treated for maxillary transverse deficiency using surgically assisted rapid maxillary/palatal expansion (SARME/SARPE) under general anesthesia. The classification of the complications aimed to assess the difficulty of their treatment as well as estimate its real cost. Methods: The retrospective study covered 185 patients who underwent surgery for a skeletal deformity in the form of maxillary constriction or in which maxillary constriction was one of its components treated by a team of maxillofacial surgeons at one center (97 females and 88 males, aged 15 to 47 years, mean age 26.1 years). Complications were divided into two groups: early complications (up to 3 weeks after surgery) and late complications (>3 weeks after surgery). In relation to the occurrence of complications, we analyzed the demographic characteristics of the group, type of skeletal deformity (class I, II, III), presence of open bite and asymmetry, surgical technique, type and size of appliance used for maxillary expansion, as well as the duration of surgery. Results: In the study group, complications were found in 18 patients (9.73%). Early complications were found in nine patients, while late complications were also found in nine patients. Early complications include no possibility of distraction, palatal mucosa necrosis, perforation of the maxillary alveolar process caused by the distractor and asymmetric distraction. Late complications include maxillary incisor root resorption, no bone formation in the distraction gap, and maxillary incisor necrosis. None of the patients required prolonged hospitalization and only one required reoperation. Conclusions: Complications were found in 18 patients (9.73%). All challenges were classified as minor difficulties since they did not suppress the final outcome of the treatment of skeletal malocclusion. However, the complications that did occur required additional corrective measures. Surgically assisted rapid maxillary expansion, when performed properly and in correlation with the correct orthodontic treatment protocol, is an effective and predictable technique for treating maxillary constriction.

Distraction-aware hierarchical learning for vascular structure segmentation in intravascular ultrasound images.

Vascular structure segmentation in intravascular ultrasound (IVUS) images plays an important role in pre-procedural evaluation of percutaneous coronary intervention (PCI). However, vascular structure segmentation in IVUS images has the challenge of structure-dependent distractions. Structure-dependent distractions are categorized into two cases, structural intrinsic distractions and inter-structural distractions. Traditional machine learning methods often rely solely on low-level features, overlooking high-level features. This way limits the generalization of these methods. The existing semantic segmentation methods integrate low-level and high-level features to enhance generalization performance. But these methods also introduce additional interference, which is harmful to solving structural intrinsic distractions. Distraction cue methods attempt to address structural intrinsic distractions by removing interference from the features through a unique decoder. However, they tend to overlook the problem of inter-structural distractions. In this paper, we propose distraction-aware hierarchical learning (DHL) for vascular structure segmentation in IVUS images. Inspired by distraction cue methods for removing interference in a decoder, the DHL is designed as a hierarchical decoder that gradually removes structure-dependent distractions. The DHL includes global perception process, distraction perception process and structural perception process. The global perception process and distraction perception process remove structural intrinsic distractions then the structural perception process removes inter-structural distractions. In the global perception process, the DHL searches for the coarse structural region of the vascular structures on the slice of IVUS sequence. In the distraction perception process, the DHL progressively refines the coarse structural region of the vascular structures to remove structural distractions. In the structural perception process, the DHL detects regions of inter-structural distractions in fused structure features then separates them. Extensive experiments on 361 subjects show that the DHL is effective (e.g., the average Dice is greater than 0.95), and superior to ten state-of-the-art IVUS vascular structure segmentation methods.

The effects of SDF-1 combined application with VEGF on femoral distraction osteogenesis in rats.

Bone regeneration and mineralization can be achieved by means of distraction osteogenesis (DO). In the present study, we investigated the effect of stromal cell-derived factor 1 (SDF-1) and vascular endothelial growth factor (VEGF) on the new bone formation during DO in rats. Forty-eight Sprague-Dawley rats were randomized into four groups of 12 rats each. We established the left femoral DO model in rats and performed a mid-femoral osteotomy, which was fixed with an external fixator. DO was performed at 0.25 mm/12 h after an incubation period of 5 days. Distraction was continued for 10 days, resulting in a total of 5 mm of lengthening. After distraction, the solution was locally injected into the osteotomy site, once a day 1 ml for 1 week. One group received the solvent alone and served as the control, and the other three groups were treated with SDF-1, VEGF, and SDF-1with VEGF in an aqueous. Sequential X-ray radiographs were taken two weekly. The regeneration was monitored with the use of micro-CT analysis, mechanical testing, and histology. Radiographs showed accelerated regenerate ossification in the SDF-1, VEGF, and SDF-1 with the VEGF group, with a larger amount of new bone compared with the control group, especially SDF-1 with the VEGF group. Micro-CT analysis and biomechanical tests showed Continuous injection of the SDF-1, VEGF, and SDF-1 with VEGF during the consolidation period significantly increased bone mineral density bone volume, mechanical maximum loading, and bone mineralization of the regenerate. Similarly, the expression of osteogenic-specific genes, as determined by real-time polymerase chain reaction , was significantly higher in SDF-1 with the VEGF group than in the other groups. Histological examination revealed more new trabeculae in the distraction gap and more mature bone tissue for the SDF-1 with the VEGF group. SDF-1 and VEGF promote bone regeneration and mineralization during DO, and there is a synergistic effect between the SDF-1 and VEGF. It is possible to provide a new and feasible method to shorten the period of treatment of DO.

Corrigendum: Virtual reality in managing dental pain and anxiety: a comprehensive review.

[This corrects the article DOI: 10.3389/fmed.2023.1285142.].

Real-world crash configurations and traffic violations among newly licensed young drivers with different route familiarity levels.

OBJECTIVE: Young drivers aged 24 and below are at heightened risks of being influenced by their route familiarity levels. This study aims to compare prevalences of crash culpability, crash configurations and risky driver behaviors among newly licensed young drivers when they are driving on roads with different route familiarity levels. METHODS: Based on the road traffic crash and violation data in Yunnan Province of China from January 2017 through December 2019, we classified drivers' different route familiarity levels by utilizing spatial distance away from residence-based method, including driving on high route familiarity (HRF) and low route familiarity (LRF) roads. Prevalence ratios were estimated using generalized estimating equation log-binomial regression models. RESULTS: We identified 12016 newly licensed young drivers driving on HRF roads and 2189 drivers on LRF roads. Within 48 months of licensure, young drivers on LRF roads were more likely to be at fault for their motor vehicle crashes than those on HRF roads. Young drivers on LRF roads were more likely to be with failure to obey traffic control device, with failure to yield right of way, wrong way driving, backing unsafely and improper parking compared with those on HRF roads. Drivers on LRF roads were less likely to be inattentive and driving with unsafe speed and following too closely compared with those on HRF roads. CONCLUSIONS: Several basic aspects of targeted countermeasures can be put forward. Visual impacts such as rectangular rapid-flashing beacon (RRFB) can be used in order to prevent wrong way driving on the tourist roadways. Arranging safety talks and programs in colleges and universities and technical interventions like Advanced Driver Assistance Systems (ADAS) can be used to reduce young drivers' driving distraction and overconfidence. It is recommended that the driving schools can use these research findings to include in licensure program to make young drivers more aware of the various factors that expose them to crash risks so that more defensive driving may be needed under different situations, and this can also help build the graduated driving licensure (GDL) programme in China.

Effects of executive load on crashes and near-crashes for young versus older drivers.

With the increasing use of infotainment systems in vehicles, secondary tasks requiring executive demand may increase crash risk, especially for young drivers. Naturalistic driving data were examined to determine if secondary tasks with increasing executive demand would result in increasing crash risk. Data were extracted from the Second Strategic Highway Research Program Naturalistic Driving Study, where vehicles were instrumented to record driving behavior and crash/near-crash data. executive and visual-manual tasks paired with a second executive task (also referred to as dual executive tasks) were compared to the executive and visual-manual tasks performed alone. Crash/near-crash odds ratios were computed by comparing each task condition to driving without the presence of any secondary task. Dual executive tasks resulted in greater odds ratios than those for single executive tasks. The dual visual-manual task odds ratios did not increase from single task odds ratios. These effects were only found in young drivers. The study shows that dual executive secondary task load increases crash/near-crash risk in dual task situations for young drivers. Future research should be conducted to minimize task load associated with vehicle infotainment systems that use such technologies as voice commands.

Tissue response following implantation with the posterior dynamic distraction device (PDDD) in adolescent idiopathic scoliosis (AIS).

PURPOSE: The PDDD is a ratchet-based, unidirectional expandable rod to treat adolescent idiopathic scoliosis (AIS), primarily by correcting scoliotic deformity without full spinal fusion. We hypothesized that the device will be fully tolerated by the host and, if aseptic screw loosening occurs, it will be unrelated to wear particle formation. METHODS: This study comprised tissue samples from seven patients from a prospective study (NCT04296903) to assess the PDDD's safety and benefits, reoperated due to complications. Host response was assessed from histological slides (four levels/implant) in accordance with GLP and ISO10993-6:2016. The elementary chemical composition of wear particles present in tissue sections was quantified by energy dispersive X-ray spectroscopy (EDX). RESULTS: Host reaction was minor, characterized by low levels of diverse inflammatory cells, mild fibrosis, occasional small necrotic foci, neovascularization, hemorrhage, and, rarely, small bone fragments. Twenty-four of 28 tissue sections displayed varying degrees of wear particles (black discoloration), and most sections (17) were scored as 1 (< 25% of the sample). The discoloration observed corresponded to black-appearing, fine granular pigment. EDX analysis confirmed particles were composed of titanium, aluminum, and vanadium. Twenty-six of 28 samples were scored zero for necrosis and 2/28 were scored 1. Eleven samples were scored zero for fibrosis, 12 as 1, and five as 2. No aseptic screw loosening occurred. CONCLUSION: The PDDD induced minimal host reaction with little or no degeneration, inflammation or fibrosis. No changes present could be expected to promote device failure. The PDDD implant for treating AIS is well-tolerated and locally safe.

Bone Regenerate Evaluation Methods.

Since its introduction by Ilizarov, the distraction osteogenesis technique has been used to treat trauma-related conditions, infections, bone tumors, and congenital diseases, either as methods of bone transport or elongation. One of the major dilemmas for the orthopedic surgeon who performs osteogenic distraction is establishing a reproducible method of assessing the progression of the osteogenesis, enabling the early detection of regenerate failures, in order to effectively interfere during treatment, and to determine the appropriate time to remove the external fixator. Several quantitative monitoring methods to evaluate the structural recovery and biomechanical properties of the bone regenerate at different stages, as well as the bone healing process, are under study. These methods can reveal data on bone metabolism, stiffness, bone mineral content, and bone mineral density. The present review comprehensively summarizes the most recent techniques to assess bone healing during osteogenic distraction, including conventional radiography and pixel values in digital radiology, ultrasonography, bone densitometry and scintigraphy, quantitative computed tomography, biomechanical evaluation, biochemical markers, and mathematical models. We believe it is crucial to know the different methods currently available, and we understand that using several monitoring methods simultaneously can be an ideal solution, pointing to a future direction in the follow-up of osteogenic distraction.

H Vessel Formation as a Marker for Enhanced Bone Healing in Irradiated Distraction Osteogenesis.

In the setting of bone defects, the injured vasculature and loss of hemodynamic inflow leads to hematoma formation and low oxygen tension which stimulates vascular expansion through the HIf-1α pathway. Most importantly, this pathway upregulates sprouting of type H vessels (CD31hiEmcnhi vessels). H vessels engage in direct interaction with perivascular osteoprogenitor cells (OPCs), osteoblasts, and preosteoclasts of bone formation and remodeling. This angiogenic-osteogenic coupling leads to synchronous propagation of vascular and bony tissue for regenerative healing. A growing body of literature demonstrates that H vessels constitute a large portion of bone's innate capacity for osteogenic healing. We believe that CD31hiEmcnhi vessels play a role in bone healing during distraction osteogenesis (DO). DO is a procedure that utilizes traction forces to facilitate induction of endogenous bone formation and regeneration of surrounding soft tissues such as skin, muscle, tendon, and neurovascular structures. While the H vessel response to mechanical injury is adequate to facilitate healing in normal healthy tissue, it remains inadequate to overcome the devastation of radiation. We posit that the destruction of CD31hiEmcnhi vessels plays a role in precluding DO's effectiveness in irradiated bone defect healing. We aim, therefore, to recapitulate the normal pathway of bony healing by utilizing the regenerative capacity of H vessels. We hypothesize that using localized application of deferoxamine (DFO) will enhance the H vessel-mediated vasculogenic response to radiation damage and ultimately enable osteogenic healing during DO. This discovery could potentially be exploited by developing translational therapeutics to hopefully accelerate bone formation and shorten the DO consolidation period, thereby potentially expanding DO's utilization in irradiated bone healing. Sprague-Dawley rats were divided into three groups: DO, radiation with DO (xDO), and radiation with DO and DFO implantation (xDODFO). Experimental groups received 35 Gy of radiation. All groups underwent DO. The treatment group received injections into the osteotomy site, every other day, beginning on postoperative day (POD) 4 of DFO. Animals were sacrificed on POD 40. For immunohistochemical analysis, mandibles were dissected and fixed in 4% paraformaldehyde for 48 hours, decalcified in Cal-Ex II for 2 days, dehydrated through graded ethanol of increasing concentration, and then embedded in paraffin. Samples were cut into 7-µm thick longitudinally oriented sections including the metaphysis and diaphysis. CD31 and Emcn double immunofluorescent staining were performed to evaluate the extent of CD31hiEmcnhi vessel formation. Bone sections were then stained with conjugated antibodies overnight at 4°C. Nuclei were stained with Hoechst. Slides were also double stained with Osterix and CD31 to study the quantity of H vessel-mediated recruitment of OPCs to accelerate bone healing. Images were acquired with a Nikon Ti2 widefield microscope and analyzed in NIS- Elements Advanced Research 5.41.02 software. The abundance of type H vessels is represented by the area fraction of CD31 + Emcn+ vessel area inside the regenerate sample. OPC concomitant proliferation into the distraction gap is represented by the area fraction of Osterix+ cell area inside of the regenerate sample. There were 6× more type H vessels in DO groups than in xDO groups. Localized DFO significantly increased the abundance of type H vessels of irradiated DO animals compared to xDO by 15× ( p = 0.00133531). Moreover, the DO and xDODFO groups with higher abundance of type H vessels also demonstrated better angiogenesis and osteogenesis outcomes. Interestingly, xDODFO groups doubled the quantity of H vessel formation compared to DO, indicating a supraphysiologic response ( p = 0.044655055). Furthermore, H vessel-mediated recruitment of OPCs mimicked the described H vessel formation trend in our study groups. Irradiated DO groups contained 3× less OPCs compared to DO controls. DFO treatment to xDO animals remediated irradiation damage by containing 12× Osterix+ cells. Finally, DFO treatment of irradiated animals quadrupled osteoprogenitor recruitment into the distraction gap compared to DO controls. In this study, we developed a novel approach to visualize CD31hiEmcnhi in paraffin sections to study DO regeneration. Normal DO demonstrated a significant upregulation of H vessel formation and associated angiogenic-osteogenic coupling. Radiation severely decreased H vessel formation along with an associated significant diminution of new bone formation and nonunion. DFO administration, however, resulted in vascular replenishment and the restoration of high quantities of CD31hiEmcnhi and OPCs, recapitulating the normal process of bony regeneration and repair. DFO treatment remediated new bone formation and bony union in irradiated fields associated with increased H vessel angiogenic-osteogenic coupling. While further studies are required to optimize this approach, the results of this study are incredibly promising for the long-awaited translation of localized DFO into the clinical arena.

Skeletal expansion via craniofacial distraction osteogenesis technique in syndromic craniosynostosis: impact on ophthalmic parameters.

BACKGROUND: This study aims to compare the changes in ophthalmic parameters among syndromic craniosynostosis patients who underwent craniofacial skeletal expansion procedures via distraction osteogenesis (DO). METHOD: A retrospective study was conducted involving syndromic craniosynostosis patients who underwent surgical expansion via the DO technique from the year 2012 to March 2022. Changes in six parameters which consist of visual acuity, refractive error, optic disc health, intraocular pressure, degree of proptosis and orbital volume were measured objectively pre and post-surgery. For categorical parameters, the Chi-square cross-tab test was done. Paired sample T-test was used for normally distributed variables. Wilcoxon signed-rank test was used for non-normally distributed data. RESULTS: Visual impairment was present in 21.4% of eyes before surgery and increased to 28.5% post-surgery. Three patients had changes of refractive error post-surgery with one developed hypermetropia, another developed anisometropia and the last had improvement to no refractive error. Two patients had optic disc swelling which was resolved post-surgery. Intraocular pressure changes were inconsistent post-surgery. All patients achieved a significant reduction in the degree of proptosis post-surgery. Orbital volume calculation using computed tomography (CT) scans shows a significant increase in volume post-surgery for all patients. CONCLUSION: Our study shows a significant increase in orbital volume post-surgery with a reduction in the degree of proptosis. Optic disc and nerve health improved after the surgery. Changes in terms of visual acuity, refractive error and IOP were inconsistent after the surgical intervention.