Interferon-α receptor antisense oligonucleotides reduce neuroinflammation and neuropathology in a mouse model of cerebral interferonopathy.

Chronic and elevated levels of the antiviral cytokine IFN-α in the brain are neurotoxic. This is best observed in patients with genetic cerebral interferonopathies such as Aicardi-Goutières syndrome. Cerebral interferonopathies typically manifest in early childhood and lead to debilitating disease and premature death. There is no cure for these diseases with existing treatments largely aimed at managing symptoms. Thus, an effective therapeutic strategy is urgently needed. Here, we investigated the effect of antisense oligonucleotides targeting the murine IFN-α receptor (Ifnar1 ASOs) in a transgenic mouse model of cerebral interferonopathy. Intracerebroventricular injection of Ifnar1 ASOs into transgenic mice with brain-targeted chronic IFN-α production resulted in a blunted cerebral interferon signature, reduced neuroinflammation, restoration of blood-brain barrier integrity, absence of tissue destruction, and lessened neuronal damage. Remarkably, Ifnar1 ASO treatment was also effective when given after the onset of neuropathological changes, as it reversed such disease-related features. We conclude that ASOs targeting the IFN-α receptor halt and reverse progression of IFN-α-mediated neuroinflammation and neurotoxicity, opening what we believe to be a new and promising approach for the treatment of patients with cerebral interferonopathies.

Evaluation of a decentralized investigational drug service pharmacist in a cancer clinical trial infusion unit.

INTRODUCTION: Investigational drug service (IDS) oversees and manages use of investigational products. There is limited data on utility of pharmacy services in clinical trial conduct and outcomes, specifically on the value of a decentralized IDS pharmacist. METHODS: This is a quasi-experimental study conducted in an oncology clinical trial infusion unit. A retrospective chart review was done to reflect current practice from January through June 2022. A decentralized IDS pharmacist was piloted in December 2022. Data collected included number and types of consults, personnel requesting the consult, and intervention performed. A satisfaction questionnaire was conducted after the pilot program. RESULTS: A total of 16.3% (173 of 1062 patient visits) of pharmacy consults were completed in the centralized IDS pharmacy model, while 44.5% (81 of 182 patient visits) of pharmacy consults were completed during the decentralized IDS pharmacist pilot, p < .001. Decentralized IDS pharmacist completed 77% (62/81) of the consults during the pilot period. Most common types of consults were toxicity management (20%), electronic medical record issues (17%), and tubing and drug administration issues (16%). More than 80% of respondents to the satisfaction questionnaire responded that implementation of a decentralized IDS pharmacist is acceptable, appropriate, and feasible. CONCLUSION: This pilot study demonstrated that a decentralized IDS pharmacist in an oncology clinical trial infusion unit improved accessibility to an IDS pharmacist, increased pharmacy consults relevant to patient care and optimized centralized pharmacists medication distribution workflow. Further studies are needed to evaluate patient benefits from implementing decentralized IDS pharmacist in direct patient care activities.

Antisense oligonucleotide-based targeting of Tau-tubulin kinase 1 prevents hippocampal accumulation of phosphorylated tau in PS19 tauopathy mice.

Tau tubulin kinase-1 (TTBK1), a neuron-specific tau kinase, is highly expressed in the entorhinal cortex and hippocampal regions, where early tau pathology evolves in Alzheimer's disease (AD). The protein expression level of TTBK1 is elevated in the cortex brain tissues with AD patients compared to the control subjects. We therefore hypothesized that antisense oligonucleotide (ASO) based targeting Ttbk1 could prevent the accumulation of phosphorylated tau, thereby delaying the development of tau pathology in AD. Here we show that in vivo administration of ASO targeting mouse Ttbk1 (ASO-Ttbk1) specifically suppressed the expression of Ttbk1 without affecting Ttbk2 expression in the temporal cortex of PS19 tau transgenic mice. Central administration of ASO-Ttbk1 in PS19 mice significantly reduced the expression level of representative phosphor-tau epitopes relevant to AD at 8 weeks post-dose, including pT231, pT181, and pS396 in the sarkosyl soluble and insoluble fractions isolated from hippocampal tissues as determined by ELISA and pS422 in soluble fractions as determined by western blotting. Immunofluorescence demonstrated that ASO-Ttbk1 significantly reduced pS422 phosphorylated tau intensity in mossy fibers region of the dentate gyrus in PS19 mice. RNA-sequence analysis of the temporal cortex tissue revealed significant enrichment of interferon-gamma and complement pathways and increased expression of antigen presenting molecules (Cd86, Cd74, and H2-Aa) in PS19 mice treated with ASO-Ttbk1, suggesting its potential effect on microglial phenotype although neurotoxic effect was absent. These data suggest that TTBK1 is an attractive therapeutic target to suppress TTBK1 without compromising TTBK2 expression and pathological tau phosphorylation in the early stages of AD.

A roadmap of craniofacial growth modification for children with sleep-disordered breathing: a multidisciplinary proposal.

Craniofacial modification by orthodontic techniques is increasingly incorporated into the multidisciplinary management of sleep-disordered breathing in children and adolescents. With increasing application of orthodontics to this clinical population it is important for healthcare providers, families, and patients to understand the wide range of available treatments. Orthodontists can guide craniofacial growth depending on age; therefore, it is important to work with other providers for a team-based approach to sleep-disordered breathing. From infancy to adulthood the dentition and craniofacial complex change with growth patterns that can be intercepted and targeted at critical time points. This article proposes a clinical guideline for application of multidisciplinary care with emphasis on dentofacial interventions that target variable growth patterns. We also highlight how these guidelines serve as a roadmap for the key questions that will influence future research directions. Ultimately the appropriate application of these orthodontic techniques will not only provide an important therapeutic option for children and adolescents with symptomatic sleep-disordered breathing but may help also mitigate or prevent its onset.

Heritability of maxillary dental cephalometric variables among monozygotic twins, dizygotic twins and their siblings.

OBJECTIVES: The purpose of this study was to investigate the heritability of dental cephalometric variables by analyzing vertical linear measurements and angular measurements of the upper incisor, canine, and first molar. MATERIALS AND METHODS: Among the 553 Korean patients who participated in twin studies conducted at Samsung Medical Center, 150 patients had their lateral cephalometric radiograph data included in this study. The group was comprised of 36 monozygotic (MZ) twins (males, 16 pairs; females, 20 pairs), 13 dizygotic (DZ) twins (males, 7 pairs; females, 6 pairs), and 26 same-sex sibling pairs (males, 11 pairs; females, 15 pairs). All patients were over 20 years old with a mean age of 39.75 years. Lateral cephalometric diagrams and linear measurements (6 vertical factors, 6 horizontal factors) were taken. Three axial planes were measured for each tooth; intraclass correlation coefficients (ICCs) were obtained for each group and heritability was calculated using Falconer's method. RESULTS: ICCs of vertical linear measurements (average 0.837, P < 0.01) and the tooth axis of the central incisor and canine (average 0.679, P < 0.001) were higher in the MZ group compared to the DZ and sibling groups; thus, these variables showed high heritability. CONCLUSIONS: Orthodontic treatment aiming to alter the tooth axis of the maxillary central incisor or canine or other vertical factors with greater heritability can be difficult, requiring strategic treatment planning to achieve desired treatment outcome and stability. CLINICAL RELEVANCE: The active early treatment to gain tooth eruption space can lead to normal tooth position.

Epigenetic Regulation of NGF-Mediated Osteogenic Differentiation in Human Dental Mesenchymal Stem Cells.

Nerve growth factor (NGF) is the best-characterized neurotrophin and is primarily recognized for its key role in the embryonic development of the nervous system and neuronal cell survival/differentiation. Recently, unexpected actions of NGF in bone regeneration have emerged as NGF is able to enhance the osteogenic differentiation of mesenchymal stem cells. However, little is known regarding how NGF signaling regulates osteogenic differentiation through epigenetic mechanisms. In this study, using human dental mesenchymal stem cells (DMSCs), we demonstrated that NGF mediates osteogenic differentiation through p75NTR, a low-affinity NGF receptor. P75NTR-mediated NGF signaling activates the JNK cascade and the expression of KDM4B, an activating histone demethylase, by removing repressive H3K9me3 epigenetic marks. Mechanistically, NGF-activated c-Jun binds to the KDM4B promoter region and directly upregulates KDM4B expression. Subsequently, KDM4B directly and epigenetically activates DLX5, a master osteogenic gene, by demethylating H3K9me3 marks. Furthermore, we revealed that KDM4B and c-Jun from the JNK signaling pathway work in concert to regulate NGF-mediated osteogenic differentiation through simultaneous recruitment to the promoter region of DLX5. We identified KDM4B as a key epigenetic regulator during the NGF-mediated osteogenesis both in vitro and in vivo using the calvarial defect regeneration mouse model. In conclusion, our study thoroughly elucidated the molecular and epigenetic mechanisms during NGF-mediated osteogenesis.

Statistical methods for Mendelian models with multiple genes and cancers.

Risk evaluation to identify individuals who are at greater risk of cancer as a result of heritable pathogenic variants is a valuable component of individualized clinical management. Using principles of Mendelian genetics, Bayesian probability theory, and variant-specific knowledge, Mendelian models derive the probability of carrying a pathogenic variant and developing cancer in the future, based on family history. Existing Mendelian models are widely employed, but are generally limited to specific genes and syndromes. However, the upsurge of multigene panel germline testing has spurred the discovery of many new gene-cancer associations that are not presently accounted for in these models. We have developed PanelPRO, a flexible, efficient Mendelian risk prediction framework that can incorporate an arbitrary number of genes and cancers, overcoming the computational challenges that arise because of the increased model complexity. We implement an 11-gene, 11-cancer model, the largest Mendelian model created thus far, based on this framework. Using simulations and a clinical cohort with germline panel testing data, we evaluate model performance, validate the reverse-compatibility of our approach with existing Mendelian models, and illustrate its usage. Our implementation is freely available for research use in the PanelPRO R package.

Impact of rapid palatal expansion on the size of adenoids and tonsils in children.

INTRODUCTION: Adenoid and tonsillar hypertrophy in children often leads to adverse respiratory symptoms and obstructive sleep apnea (OSA). Current clinical guidelines from the American Academy of Pediatrics and American Academy of Otolaryngology-Head and Neck Surgery recommend tonsillectomy as the first line of pediatric OSA treatment for children with tonsillar hypertrophy. Rapid palatal expansion (RPE) performed by orthodontists improves obstructive sleep apnea in children by reducing nasal airway resistance, increasing nasal volume, raising tongue posture, and enlarging pharyngeal airway. However, the role of RPE in alleviating adenoid and tonsillar hypertrophy remains elusive. In this study, we aim to evaluate the changes in adenoid and palatine tonsil sizes following RPE using 3D volumetric analysis of cone beam computational tomography (CBCT) imaging. MATERIALS AND METHODS: In this retrospective cohort study, a total of 60 pediatric patients (mean age: 8.00, range: 5-15, 32 females and 28 males) who had tonsillar hypertrophy (size 3 and 4) were included and divided into the control group (n = 20) and expansion group (n = 40). The control group did not undergo any treatment. The expansion group underwent RPE using a conventional Hyrax expander, activated 0.25 mm per day for 4-6 weeks. Final CBCT scans (T2) were performed 13.8 ± 6.5 months after the initial scan (T1). Pediatric sleep questionnaire (PSQ) and BMI were obtained at each timepoint. Volumetric analysis of adenoid and palatine tonsils was performed using a combination of bony and soft tissue landmarks in CBCT scans through Anatomage Invivo 6 imaging software. Paired t-tests were used to evaluate the difference between the initial and final adenoid and tonsil volumes. p values less than 0.05 were considered statistically significant. RESULTS: Compared to the control group, the expansion group experienced a statistically significant decrease in both adenoid and tonsil volume. There was non-statistically significant increase in volume from T1 to T2 for the control group. For the expansion group, 90.0% and 97.5% of patients experienced significant reduction in adenoid and tonsil volume, respectively. The average volume decrease of adenoids was 16.8% while that of tonsils was 38.5%. The patients had up to 51.6% and 75.4% reduction in adenoid and tonsil size, respectively, following RPE orthodontic treatment. Pearson correlation ranged from 0.88 to 0.99 for each measurement, representing excellent internal consistency. There was a significant reduction in the PSQ scores from 5.81 ± 3.31 to 3.75 ± 2.38 in expansion group (p < 0.001). CONCLUSIONS: Our results demonstrated that RPE significantly reduced the size of both adenoid and palatine tonsils and revealed another long-term benefit of RPE treatment. To our knowledge, this is the first study to quantify the changes of adenoids and tonsils following RPE. RPE treatment can be considered as a valid and effective treatment option for pediatric OSA population with narrow high arch palate and adenotonsillar hypertrophy.

Indigenous microbiota protects development of medication-related osteonecrosis induced by periapical disease in mice.

Bacterial infection is a common finding in patients, who develop medication-related osteonecrosis of the jaw (MRONJ) by the long-term and/or high-dose use of anti-resorptive agents such as bisphosphonate (BPs). However, pathological role of bacteria in MRONJ development at the early stage remains controversial. Here, we demonstrated that commensal microbiota protects against MRONJ development in the pulp-exposed periapical periodontitis mouse model. C57/BL6 female mice were treated with intragastric broad-spectrum antibiotics for 1 week. Zoledronic acid (ZOL) through intravenous injection and antibiotics in drinking water were administered for throughout the experiment. Pulp was exposed on the left maxillary first molar, then the mice were left for 5 weeks after which bilateral maxillary first molar was extracted and mice were left for additional 3 weeks to heal. All mice were harvested, and cecum, maxilla, and femurs were collected. ONJ development was assessed using µCT and histologic analyses. When antibiotic was treated in mice, these mice had no weight changes, but developed significantly enlarged ceca compared to the control group (CTL mice). Periapical bone resorption prior to the tooth extraction was similarly prevented when treated with antibiotics, which was confirmed by decreased osteoclasts and inflammation. ZOL treatment with pulp exposure significantly increased bone necrosis as determined by empty lacunae and necrotic bone amount. Furthermore, antibiotics treatment could further exacerbate bone necrosis, with increased osteoclast number. Our findings suggest that the commensal microbiome may play protective role, rather than pathological role, in the early stages of MRONJ development.

The ERα/KDM6B regulatory axis modulates osteogenic differentiation in human mesenchymal stem cells.

Osteoporosis is a highly prevalent public health burden associated with an increased risk of bone fracture, particularly in aging women. Estrogen, an important medicinal component for the preventative and therapeutic treatment of postmenopausal osteoporosis, induces osteogenesis by activating the estrogen receptor signaling pathway and upregulating the expression of osteogenic genes, such as bone morphogenetic proteins (BMPs). The epigenetic regulation of estrogen-mediated osteogenesis, however, is still unclear. In this report, we found that estrogen significantly induced the expression of lysine-specific demethylase 6B (KDM6B) and that KDM6B depletion by shRNAs led to a significant reduction in the osteogenic potential of DMSCs. Mechanistically, upon estrogen stimulation, estrogen receptor-α (ERα) was recruited to the KDM6B promoter, directly enhancing KDM6B expression. Subsequently, KDM6B was recruited to the BMP2 and HOXC6 promoters, resulting in the removal of H3K27me3 marks and activating the transcription of BMP2 and HOXC6, the master genes of osteogenic differentiation. Furthermore, we found that estrogen enhanced DMSC osteogenesis during calvarial bone regeneration and that estrogen's pro-osteogenic effect was dependent on KDM6B in vivo. Taken together, our results demonstrate the vital role of the ERα/KDM6B regulatory axis in the epigenetic regulation of the estrogen-dependent osteogenic response.

Compounding sterile products during a personal protective equipment shortage.

PURPOSE: To describe our pharmacy department's plan for conservation of personal protective equipment (PPE) during the coronavirus disease 2019 (COVID-19) pandemic to ensure continued availability of sterile compounded products. SUMMARY: PPE shortages impacted hospitals throughout the nation in the early months of the COVID-19 pandemic response. The PPE requirement for sterile compounding and need to maintain supplies within the pharmacy cleanroom are often overlooked. A sustained supply of PPE is critical to ensure an uninterrupted supply of compounded medications to our patient population. Multiple conservation strategies, including staffing changes, communication, adjustments to training, and even reuse of select PPE, can assist with conservation. CONCLUSION: PPE in pharmacy cleanrooms is critical for the continued provision of sterile compounds with appropriate beyond-use dates and effective patient care. Pharmacy departments must employ multiple conservation strategies to ensure PPE is available for continued compounding of sterile products, and early planning and implementation of conservation strategies are key.

Psychosocial outcomes following germline multigene panel testing in an ethnically and economically diverse cohort of patients.

BACKGROUND: Little is known about the psychological outcomes of germline multigene panel testing, particularly among diverse patients and those with moderate-risk pathogenic variants (PVs). METHODS: Study participants (N = 1264) were counseled and tested with a 25- or 28-gene panel and completed a 3-month postresult survey including the Multidimensional Impact of Cancer Risk Assessment (MICRA). RESULTS: The mean age was 52 years, 80% were female, and 70% had cancer; 45% were non-Hispanic White, 37% were Hispanic, 10% were Asian, 3% were Black, and 5% had another race/ethnicity. Approximately 28% had a high school education or less, and 23% were non-English-speaking. The genetic test results were as follows: 7% had a high-risk PV, 6% had a moderate-risk PV, 35% had a variant of uncertain significance (VUS), and 52% were negative. Most participants (92%) had a total MICRA score ≤ 38, which corresponded to a mean response of "never," "rarely," or only "sometimes" reacting negatively to results. A multivariate analysis found that mean total MICRA scores were significantly higher (more uncertainty/distress) among high- and moderate-risk PV carriers (29.7 and 24.8, respectively) than those with a VUS or negative results (17.4 and 16.1, respectively). Having cancer or less education was associated with a significantly higher total MICRA score; race/ethnicity was not associated with the total MICRA score. High- and moderate-risk PV carriers did not differ significantly from one another in the total MICRA score, uncertainty, distress, or positive experiences. CONCLUSIONS: In a diverse population undergoing genetic counseling and multigene panel testing for hereditary cancer risk, the psychological response corresponded to test results and showed low distress and uncertainty. Further studies are needed to assess patient understanding and subsequent cancer screening among patients from diverse backgrounds. LAY SUMMARY: Multigene panel tests for hereditary cancer have become widespread despite concerns about adverse psychological reactions among carriers of moderate-risk pathogenic variants (mutations) and among carriers of variants of uncertain significance. This large study of an ethnically and economically diverse cohort of patients undergoing panel testing found that 92% "never," "rarely," or only "sometimes" reacted negatively to results. Somewhat higher uncertainty and distress were identified among carriers of high- and moderate-risk pathogenic variants, and lower levels were identified among those with a variant of uncertain significance or a negative result. Although the psychological response corresponded to risk, reactions to testing were favorable, regardless of results.

A likelihood-based approach to assessing frequency of pathogenicity among variants of unknown significance in susceptibility genes.

Commercialized multigene panel testing brings unprecedented opportunities to understand germline genetic contributions to hereditary cancers. Most genetic testing companies classify the pathogenicity of variants as pathogenic, benign, or variants of unknown significance (VUSs). The unknown pathogenicity of VUSs poses serious challenges to clinical decision-making. This study aims to assess the frequency of VUSs that are likely pathogenic in disease-susceptibility genes. Using estimates of probands' probability of having a pathogenic mutation (ie, the carrier score) based on a family history probabilistic risk prediction model, we assume the carrier score distribution for probands with VUSs is a mixture of the carrier score distribution for probands with positive results and the carrier score distribution for probands with negative results. Under this mixture model, we propose a likelihood-based approach to assess the frequency of pathogenicity among probands with VUSs, while accounting for the existence of possible pathogenic mutations on genes not tested. We conducted simulations to assess the performance of the approach and show that under various settings, the approach performs well with very little bias in the estimated proportion of VUSs that are likely pathogenic. We also estimate the positive predictive value across the entire range of carrier scores. We apply our approach to the USC-Stanford Hereditary Cancer Panel Testing cohort, and estimate the proportion of probands that have VUSs in BRCA1/2 that are likely pathogenic to be 10.12% [95%CI: 0%, 43.04%]. This approach will enable clinicians to target high-risk patients who have VUSs, allowing for early prevention interventions.

Growth differentiation factor 6, a repressive target of EZH2, promotes the commitment of human embryonic stem cells to mesenchymal stem cells.

Mesenchymal stem cells (MSCs) derived from human embryonic stem cells (hESCs) have significant potential for cell-mediated bone regeneration. Our recent study revealed that inhibiting the epigenetic regulator EZH2 plays a key role in promoting the mesodermal differentiation of hESCs. In this study, an epigenome-wide analysis of hESCs and MSCs revealed that growth differentiation factor 6 (GDF6), which is involved in bone formation, was the most upregulated gene associated with MSCs compared to hESCs. Furthermore, we identified GDF6 as a repressive target of EZH2 and found that ectopic GDF6 selectively promoted hESC differentiation towards the mesodermal lineage and enriched the MSC population. Our results provide molecular insights governing the mesenchymal commitment of hESCs and identify an inducing factor that offers strong promise for the future of regenerative medicine.

A study on the morphologic change of palatal alveolar bone shape after intrusion and retraction of maxillary incisors.

The purpose of this study is to evaluate the changes in the palatal alveolar bone thickness and find the factors related to the resorption of the palatal alveolar bone caused by tooth movement after the maxillary incisors were retracted and intruded during orthodontic treatment. The study group comprised of 33 skeletal Class II malocclusion patients who underwent extraction for orthodontic treatment. Palatal alveolar bone thickness changes and resorption factors were identified and analyzed. The changes of maxillary central incisors and palatal alveolar bone thickness were measured, and the corresponding sample t test was performed using SPSS (IBM SPSS version 22). The amount of palatal alveolar bone resorption was measured and various parameters were analyzed to determine which factors affected it. Correlation analysis adopting the amount of palatal alveolar bone resorption as a dependent variable demonstrated that the SNB, mandibular plane angle, and the inclination of the maxillary central incisor were significantly correlated with before treatment. On the other hand, mandibular plane angle, angle of convexity, the inclination of the upper incisor, and the occlusal plane (UOP, POP) were significantly correlated with post-treatment. In addition, the variables related to palatal contour (PP to PAS, SN to PAS, palatal surface angle) and occlusal planes (UOP/POP) were significantly correlated with the difference in palatal bone resorption. During initial diagnosis, high angle class II with normal upper incisor inclination can be signs of high-risk factors. In addition, maintaining the occlusal plane during treatment helps to prevent palatal bone loss.

Alveolar bone remodeling during maxillary incisor intrusion and retraction.

BACKGROUND: Maxillary incisor protrusion is a prevalent dental deformity and is often treated by upper incisor intrusion and retraction. The mechanical loading triggers the resorption and apposition of the bone. Alveolar bone remodeling is expected to follow orthodontic tooth movement in a one-to-one relationship. However, in many cases, the outcomes are different. Alveolar bone might still remain thick causing lip protrusion and other aesthetic problems after treatment. Additional corrective procedures such as alveoloplasty. On the other hand, if the labial bone becomes too thin, periodontal problems like gingival recession might occur. The unpredictability of the treatment result and the risk of requiring corrective procedures pose significant challenges to both the providers and patients. The aim of this study is to determine factors that can help to predict the alveolar bone reaction before maxillary incisor intrusion and retraction. METHODS: The cohort included 34 female patients (mean age 25.8 years) who were diagnosed with skeletal class II malocclusion with upper incisor protrusion. These patients underwent extraction and orthodontic treatment with upper incisor intrusion and retraction. Lateral cephalograms at pre-treatment and post-treatment were taken. Linear and angular measurements were analyzed to evaluate the alveolar bone changes based on initial conditions. RESULTS: The study found that the relative change, calculated as change in alveolar bone thickness after treatment divided by the initial alveolar thickness, was inversely correlated with the initial thickness. There was a significant increase of labial alveolar bone thickness at 9-mm apical from cementoenamel junction (B3) (P < 0.05) but no statistically significant change in the thickness at other levels. In addition, the change in angulation between the incisor and alveolar bone was inversely correlated with several initial angulations: between the initial palatal plane and upper incisor angle, between the initial palatal plane and upper incisor labial surface angle, and between the initial palatal plane and bone labial surface angle. On the other hand, the change in labial bone thickness was neither significantly correlated with the initial thickness nor significantly correlated to the amount of retraction. CONCLUSION: The unpredictability of alveolar bone remodeling after upper incisor intrusion and retraction poses significant challenges to treatment planning and patient experience. The study showed that the initial angulation between the incisor and alveolar bone is correlated with the change in angulation after treatment, the initial thickness of the alveolar bone was correlated with the relative change of the alveolar bone thickness (defined as change in thickness after treatment divided by its initial thickness), and the amount of intrusion was correlated with the alveolar bone thickness change at 9-mm apical from the cementoenamel junction after treatment. The results of the present study also revealed that the change in labial alveolar bone thickness was neither significantly correlated with the initial thickness nor significantly correlated to the amount of retraction.

Correcting severe scissor bite in an adult.

Scissor bite often remains unnoticed by patients although it can adversely affect facial symmetry, jaw growth, and mastication. This case report illustrates the efficacy of temporary skeletal anchorage devices (TSADs) and a modified lingual arch in correcting severe scissor bite. A 28-year-old woman presented with severe scissor bite in the mandibular right posterior segment. To treat this condition, TSADs were used for maxillary posterior intrusion and a modified lingual arch for buccally uprighting mandibular posterior teeth. Long-term retention records demonstrate stable treatment results.

Author Correction: Single CD271 marker isolates mesenchymal stem cells from human dental pulp.

In the original version of this Article, Figure 1c was inadvertently assembled with a duplicate of Figure 1b. The correct image for Figure 1c, shown below, has been added in the HTML and PDF versions of the Article. This does not affect the conclusions of the study. We sincerely apologize for any inconvenience this may have caused our readers.