Evaluation of Arthrocentesis with hyaluronic acid injections for management of temporomandibular disorders: a systematic review and case series.

Although arthrocentesis is an accepted safe treatment modality for the management of temporomandibular disorders (TMD) in symptomatic patients, the benefit of hyaluronic acid (HA) injections remains uncertain. The aim of this study was to evaluate whether intra-articular HA injections adjunctive to arthrocentesis can be more effective than other medications for the improvement of TMD associated symptoms. Additionally, the impact of HA injections on quality of life of TMD patients was assessed with SF-36® questionnaire in a cohort of patients. An electronic search of Medline, Scopus and Cochrane databases was performed up to March 2020. The following search terms were used: "arthrocentesis", "hyaluronic acid", "intra-articular injections", "visco-supplementation", "temporomandibular disorders". Prospective and retrospective studies that reported the application of HA injections compared to other intra-articular drugs for the treatment of temporomandibular disorders were included. Systematic or narrative reviews and pre-clinical studies were excluded. Additionally, a retrospective clinical study was performed for evaluation of changes in quality of life before and after arthrocentesis with HA injections. In the systematic review, the initial search yielded 1327 articles. After screening of the titles, abstracts, and full texts, 29 studies were selected (26 randomized studies, 2 controlled clinical trials, 1 retrospective report). In the clinical study, 12 patients were included. Intra-articular injections of HA and other medications together with arthrocentesis seemed to be beneficial for improvement of functional symptoms of TMD and pain. The case series also supported the efficacy of HA injections showing an improvement of quality of life of these patients. However, from literature review, it was impossible to identify an optimum drug or a protocol for predictably improving the pain and/or functional symptoms of temporomandibular problems, due to different etiologies, diversity of treatment modalities and conflicting results. In conclusion, there is no consensus in the literature that HA injections shows better results in comparison with other treatment modalities. According to the results of the present clinical study, HA injections with/without arthrocentesis seems to be beneficial in terms of clinical symptoms and quality of life of the TMD patients.

Contribution of Indian researchers in high impact periodontal journals: a bibliometric analysis of last three years.

Bibliometric Analysis researches and analyses the quantitative data derived from scientific publications through the empirical evidence of scientific activity generated by collaborating authors through the final product of their research: the scientific article. In scientific society, the concept of impact factor is probably the most widely used in bibliometric construction. To assess the scientometrics of three high-impact factor periodontal journals and identify the contribution of India in these most productive journals over three years (Jan 2018 - Dec 2020) and to know the most influential topics researched. A retrospective observational study was conducted for the Journal of Clinical Periodontology, Journal of Periodontology, and Journal of Periodontal Research. All issues of 2018, 2019, and 2020 were electronically and hand searched for the following parameters: Number of papers, affiliated organizations, and countries, topics reported, and contribution of Indian authors. The data were organized and analyzed with descriptive statistics using SPSS software (version 21.0). In total 469 articles were published by Journal of Periodontology, followed by 454 articles in Journal of Clinical Periodontology and 287 articles in Journal of Periodontal Research. In all the three journals, China had the maximum contributions, succeeded by USA. India has published maximum number of articles in the Journal of Periodontal Research. When analysed, although less as compared to the western counterparts, an increasing trend in the publications is seen in case of India.

Knowledge, practices and perceptions regarding oral health preventive measures among Mexican dental students: a cross-sectional survey study.

Although oral diseases are mostly preventable, they remain a global public health problem. Thus, there is a need for trained personnel to actively intervene in promoting oral health, to prevent and timeously detect oral diseases, and, in turn, to provide comprehensive quality healthcare. The main objective of the study was to evaluate the knowledge, practices and perceptions regarding oral health preventive measures amongst undergraduate dental students. This cross-sectional study was conducted between the period October 2017 and January 2018. The subjects included were undergraduate students of the dental science program at the School of Dentistry, in Leon Guanajuato, Mexico. A validated questionnaire was used to identify knowledge of preventive dentistry and the frequency of oral health preventive actions in the dental school clinics. Besides, perception towards prevention in dentistry was assessed. A total of N=232 undergraduate students participated of whom 65.9% (N=153) were women. More than half of the students 59.5%, (N=138) rated their knowledge on the prevention of oral diseases as good, followed by 32.8% (N=75) of students who rated it as regular. 49% (N=97) of the students performed frequently preventive treatments in their daily clinical practice. 90% (N=217) think that the main reason of low practice of prevention in dentistry is the lack of commitment of the dentist. 72.8% (N=169) mention that there should be professionals dedicated exclusively to preventive dentistry. Students of second grade demonstrated better prevention knowledge and tended to engage more frequently in preventive activities (p<0.05). In conclusion, our study found that, second-year students perform preventive practices more frequently and these practices decrease as their studies progress. It should be sought to create positive attitudes towards prevention not only in the year in preventive dentistry, but also throughout the entire career. This enables students to become trained professionals that can deliver preventive services to their patients.

Transverse maxillary deficit and its influence on the cervical vertebrae maturation index.

AIM: The aim of this study is to evaluate whether a transverse maxillary deficit can cause an alteration of vertebral development and therefore of the skeletal maturation comparing the cervical maturation stages index with the hand-wrist index. MATERIALS AND METHODS: For the study were selected 200 patients aged 7-14 years, equally distributed by gender and divided into 100 study subjects with maxillary deficit and 100 controls without maxillary deficit. The skeletal maturation index (SM according to Fishman) was evaluated and compared with the hand-wrist x-rays and the cervical vertebrae maturation (CVM according to Hassel and Farmann). RESULTS: Forty-one per cent of the subjects in the test group show a discrepancy between CVM and SM. Among these 73% (30 subjects) present an advanced stage of CVM compared with the corresponding SM. Only 16% of the subjects in the control group show a discrepancy between CVM and SM. Among these 69% (11 subjects) appear in an advanced CVM stage. CONCLUSION: The analysis of the CVM stage in subjects with transverse maxillary deficit appears to be altered compared with the SM identified through a hand-wrist x-ray. In the case of individuals with transverse maxillary deficit it is advisable to use also a hand-wrist x-ray, thus not relying only on CVM for the evaluation of the skeletal growth stages.

Pulp and periodontal healing after replantation of a maxillary immature incisor: a 13-year follow-up.

BACKGROUND: Traumatic tooth avulsions occur most often in 7 to 9 year-old children. Replantation is considered the treatment of choice and follow-up is required in order to prevent possible complications. CASE REPORT: A case of replantation of a maxillary immature incisor in a 9.2-year-old male is reported. Tooth 21 was stored in saliva, in the child's mouth, and it was replanted within 45 min following a bicycle accident. A flexible splint was applied from tooth 11 to tooth 63, and it was removed after 4 weeks. Pulp canal obliteration was diagnosed at the 6 months check-up visit. Pulp sensibility was positive after 3 months and absent after 5 years. During the follow-up the tooth completed its development and always presented a physiological mobility and a probing depth <3 mm. Only a minimal discoloration of the crown was observed. CONCLUSION: The knowledge of emergency care at the scene of dental trauma is resolutory for treatment outcome.

Relationship between mandibular second molar calcification stages and cervical vertebrae maturity in Italian children and young adults.

AIM: The aim of this study was to investigate the relationship between the stages of calcification of the mandibular second molar and the stages of skeletal maturity among Italian children and young adults. MATERIALS AND METHODS: Cross-sectional descriptive study. The samples were derived from panoramic radiographs and lateral cephalograms of 500 Italian subjects aged from 10 to 20 years. Dental maturity index (DM) was assessed by calcification stages of the mandibular second molars according to the Demirjian method; skeletal maturity was evaluated with cervical vertebrae maturation index (CVM) according to Hassel and Farman. The Pearson r coefficient and Spearman rank correlation coefficient were estimated to determine the relationship between DM and CVM. RESULTS: Skeletal maturation stages occurred earlier in females (about 6 months). A highly significant correlation between CVM and DM (0.78-0.86 cor according to Pearson test and 0.81-0.85 rho according to Spearman test) was found. DM stage E corresponds to phase CVM 1 and 2 (the phase prior to the growth spurt), DM stage F corresponds to the phase of pubertal growth spurt, stages CVM 2 and CVM 3; DM stage G is indicator of the growth spurt underway (CVM 3-4), but it can still be found during CVM 5 in females. CONCLUSION: The second mandibular molars can be considered reliable indicators for the evaluation of the growth phases. In case of females the end of the growth spurt it is not clearly associated with a dental maturity stage and needs to be stated with further parameters such as CVM.

Development and machine learning-based calibration of low-cost multiparametric stations for the measurement of CO2 and CH4 in air.

The pressing issue of atmospheric pollution has prompted the exploration of affordable methods for measuring and monitoring air contaminants as complementary techniques to standard methods, able to produce high-density data in time and space. The main challenge of this low-cost approach regards the in-field accuracy and reliability of the sensors. This study presents the development of low-cost stations for high-time resolution measurements of CO2 and CH4 concentrations calibrated via an in-field machine learning-based method. The calibration models were built based on measurements parallelly performed with the low-cost sensors and a CRDS analyzer for CO2 and CH4 as reference instrument, accounting for air temperature and relative humidity as external variables. To ensure versatility across locations, diversified datasets were collected, consisting of measurements performed in various environments and seasons. The calibration models, trained with 70 % for modeling, 15 % for validation, and 15 % for testing, demonstrated robustness with CO2 and CH4 predictions achieving R2 values from 0.8781 to 0.9827 and 0.7312 to 0.9410, and mean absolute errors ranging from 3.76 to 1.95 ppm and 0.03 to 0.01 ppm, for CO2 and CH4, respectively. These promising results pave the way for extending these stations to monitor additional air contaminants, like PM, NOx, and CO through the same calibration process, integrating them with remote data transmission modules to facilitate real-time access, control, and processing for end-users.

Three-dimensional changes of the upper airway in patients with obstructive sleep apnea syndrome after a non-adjustable oral appliance treatment.

The diagnosis, the therapy and the monitoring of the obstructive sleep apnea syndrome (OSAS) are to be considered as critical factors in order to prevent severe systemic complications that can be caused by this pathological condition. This work presents three cases of adult patients affected by OSAS, undergoing therapy with oral appliances (OAs), meant to remove the pharyngeal obstruction caused by mandibular retrusion and tongue collapse in nocturnal supine position. The aim of this work was to evaluate the effect of the OAs both through the comparison of the polysomnographic analysis, in the presence and absence of the appliance in situ, and also through the volumetric measurements of the pharingeal airway thanks to the cone beam computed tomography.

Optical coherence tomography application for assessing variation in bone mineral content: a preclinical study.

OBJECTIVE: Optical Coherence Tomography (OCT) is a non-invasive imaging technique that produces cross-sectional images through biological tissues, allowing three-dimensional reconstruction and analysis. Aim was to evaluate if OCT may discriminate among tissues with different bone density and composition, by measuring the depth of light penetration in porcine and rat bone samples. MATERIALS AND METHODS: Two carpal bone samples (2 cm length) were harvested from the porcine forelimb and fixed overnight in 3.7% buffered formal saline. Following fixation, one sample was decalcified in a 1:1 mixture of 8% hydrochloric acid and 8% formic acid solution for three days, with solution changes each day. Samples were imaged using an OCT microscope. Furthermore, the calvaria, ulnar, alveolar and basal bone of the mandible of 6 male and 6 female rats were cleared of overlying soft tissues and scanned under OCT. The light penetration depth in each sample was measured using the software Image J, and Scattering Attenuation Microscopy. RESULTS: In the mineralized bone the average depth (µm) and standard deviation (SD) of light penetration were 790.1±18.05 and 410.4±21.7 for periosteal and endosteal surface, respectively, and 507.3±21.03 for cross-section surfaces, while it was 858.4±32.03 for periosteal surface, 1150±26.9 for endosteal, and 627.3±31.8 for cross-section bone surfaces in demineralized porcine bone. There was a significant difference (p<0.001) in depth of light penetration between normal and de-mineralized bone for all regions evaluated. No systematic significant difference in light penetration depth between-gender was found at any site evaluated, while there were variations between sites (p<0.001). The OCT detected differences in bone mineral and porosity among gender (p<0.0001) CONCLUSIONS: This study suggests that OCT may represent a valuable technique to estimate local variations in bone mineral content.

Diagnosis of dental and mandibular asymmetries in children according to Levandoski Panoramic Analysis.

AIM: The purpose of this study was to evaluate the use of the Levandoski Panoramic Analysis in the diagnosis of dental and mandibular asymmetries and its contribution to clinical patient's evaluation and treatment planning. MATERIALS AND METHODS: Thirty-one randomly selected panoramic radiographs of children from 7 to 14 year old were analysed using 10 linear measurements. Right and left values were compared with Student's paired T tests. For each value, mean and standard deviation were computed separately for each side. RESULTS: Statistics. A dominance for the left side over the right side was observed. The data obtained were not statistically significant with the exception of maxillary length: the right side length of the maxilla was shorter (p<0.05) compared to the left side. CONCLUSIONS: Levandosky Panoramic Analisys represents a useful screening method in the diagnosis of dental and mandibular asymmetries.

Impact on air quality of carbon and sulfur volatile compounds emitted from hydrothermal discharges: The case study of Pisciarelli (Campi Flegrei, South Italy).

Volcanoes are currently to be regarded as natural sources of air pollutants. Climatic and environmental forcing of large volcanic eruptions are well known, although gases emitted through passive degassing during periods of quiescence or hydrothermal activity can also be highly dangerous for the environment and public health. Based on compositional and isotopic data, a survey on the spatial distribution in air of the main volatile compounds of carbon (CO2 and CH4) and sulfur (H2S and SO2) emitted from the fumarolic field of Pisciarelli (Campi Flegrei, Pozzuoli, Naples), a hydrothermal area where degassing activity has visibly increased since 2009, was carried out. The main goals of this study were (i) to evaluate the impact on air quality of these natural manifestations and (ii) inquire into the behavior of the selected chemical species once released in air, and their possible use as tracers to distinguish natural and anthropogenic sources. Keeling plot analysis of CO2 and CH4 isotopes revealed that the hydrothermal area acts as a net source of CO2 in air, whilst CH4 originated mainly from anthropogenic sources. Approaching the urban area, anthropogenic sources of CO2 increased and, at distances greater than 800 m from the Pisciarelli field, they prevailed over the hydrothermal signal. While hydrothermal CO2 simply mixed with that in the atmospheric background, H2S was possibly affected by oxidation processes. Therefore, SO2 measured in the air near the hydrothermal emissions had a secondary origin, i.e. generated by oxidation of hydrothermal H2S. Anthropogenic SO2 was recognized only in the furthest measurement site from Pisciarelli. Finally, in the proximity of a geothermal well, whose drilling was in progress during our field campaign, the H2S concentrations have reached values up to 3 orders of magnitude higher than the urban background, claiming the attention of the local authorities.

Premature loss of maxillary primary incisor and delayed eruption of its successor: report of a case.

BACKGROUND: Traumatic injuries to primary teeth represent one of the most common aetiologic factors of time-related eruption disturbances of permanent teeth. These include premature eruption, delayed eruption or impactions. CASE REPORT: A case of a 7.5-year-old male with delayed eruption of the maxillary permanent left incisor is presented. The case history revealed a trauma around the age of 3 involving its primary tooth predecessor and its extraction by a dentist about one year later due to frequent abscesses. The clinical examination showed an early mixed dentition and the single presence of tooth 11 in the dental arch, with an obvious aesthetic problem that affected the child's self image. The periapical x-ray ruled out any dimorphism on the impacted tooth, and it showed a root developed by two thirds. About 2 months after the examination, a simple gingivectomy was carried out, and the tooth could erupt completely 3 months later without any need for orthodontic traction. One year after surgery, a complete root development could be observed, as well as the presence of the lateral incisors with a moderate crowding.

A "typodont" study of rate of orthodontic space closure: self-ligating systems vs. conventional systems.

AIM: The aim of this study was to compare the effectiveness of space closure of two bracket systems, self-ligating and conventional ones, considering two systems with the same design and prescription. The experimental model of this study aims to identify in general if one type of system is more suitable for planning the extractive therapy, without considering the clinical aspect necessary for an adequate orthodontic approach. METHODS: A resin maxilla without the first premolars was used to test the self-ligating and conventional brackets system. Space closure was achieved on 0.016x0.022" in stainless steel wires with nickel-titanium coil springs 150 grams in strength and 10 mm in length. Two experiment settings have been prepared. The first setting was made bonding conventional bracket on the right side and self-ligating on the left; the last one was made bonding self-ligating bracket on the right side and conventional on the left. All measurements (runs) have been repeated seven times for both settings. RESULTS: During the closing phase of extraction spaces both systems are equable since there are no significant statistical differences (P=0.70). CONCLUSION: Our typodont model showed no significant difference in the efficiency of space closure between the self-ligating bracket and conventional bracket tied with stainless steel ligatures.

Electronic and magnetic study of polycationic Mn(12) single-molecule magnets with a ground spin state S = 11.

The preparation, magnetic characterization, and X-ray structures of two polycationic Mn(12) single-molecule magnets [Mn(12)O(12)(bet)(16)(EtOH)(4)](PF(6))(14).4CH(3)CN.H(2)O (1) and [Mn(12)O(12)(bet)(16)(EtOH)(3)(H(2)O)](PF(6))(13)(OH).6CH(3)CN.EtOH.H(2)O (2) (bet = betaine = (CH(3))(3)N(+)-CH(2)-CO(2)(-)) are reported. 1 crystallizes in the centrosymmetric P2/c space group and presents a (0:2:0:2) arrangement of the EtOH molecules in its structure. 2 crystallizes in the noncentrosymmetric P4 space group with two distinct Mn(12) polycations, [Mn(12)O(12)(bet)(16)(EtOH)(2)(H(2)O)(2)](14+) (2A) and [Mn(12)O(12)(bet)(16)(EtOH)(4)](14+) (2B) per unit cell. 2A and 2B show a (1:1:1:1) distribution of the coordinated solvent molecules. Interestingly, bond valence sum calculations extracted from X-ray diffraction data indicate the presence of two Mn(2+) ions in the Mn(12) core for both 1 and 2. This finding is confirmed by X-ray absorption spectroscopy (XAS) measurements. A complete magnetic characterization, including subkelvin micro-SQUID magnetometry and inelastic neutron scattering (INS) measurements, permits to extract the parameters of the giant spin Hamiltonian of these polycations. Compared with the archetypal Mn(12) acetate, an increase in the value of the ground spin state from S = 10 to S = 11 together with a decrease in the effective energy barrier, is observed for 1 and 2. Such a result is consistent with the reduction of two Mn(3+) to the less anisotropic Mn(2+) ion in the structures.

Sports-related dental injuries: knowledge of first aid and mouthguard use in a sample of Italian children and youngsters.

AIM: The purpose of this study was to evaluate the awareness of sports as risk factor of dental injuries, the emergency management when a tooth avulsion occurs and the compliance about mouthguards. MATERIALS AND METHODS: Two hundred children and youngsters 8- to 15-year-old (147 boys and 53 girls) attending Sports Societies in Isernia, a town in Southern Italy, participated to the investigation. The sports involved were soccer, martial arts, tennis, swimming, volleyball, basketball and cycling. The questionnaire was structured into three parts: 1) questions about age, sex, type and time of sports practice; 2) questions about dental injuries, particularly personal experience, awareness of first aid and procedure about tooth avulsion; 3) questions about knowledge and use of mouthguards. RESULTS: Sixty-five per cent of the athletes were aware of the possibility of oral injuries during sports practice and 8.5% referred an experience of dental trauma; 71.5% of the participants think that the immediate management of dental injuries by a dentist is very important to increase the rate of success; 31% know that the avulsed tooth may be reimplanted: 33.9% would reimplant the tooth within an hour and 62.9% would keep it in a wet storage medium. Finally, 80.5% of the athletes knew about mouthguards as protective devices, but only 5% actually used them; eight out of ten were provided by the dentist. CONCLUSION: Educational programs organized by the sports dentistry community are needed to inform coaches, teachers, athletes and parents about dental injuries and to promote the mouthguards use, especially in contact sports practice.

Comparative evaluation of the group of teeth with the best prediction value in the mixed dentition analysis.

AIM: Mixed dentition analysis allows the prediction of the tooth width of non erupted permanent canines and premolars (SPCP). It is an essential factor in treatment planning since it could predict a tooth-size to arch-length discrepancy. The aim of this study was to determine which group of permanent teeth presented the best prediction capability for the width sums of the unerupted canine and premolars in an Italian sample. MATERIALS AND METHODS: A total of 150 subjects with complete permanent dentition were selected. Their dental casts were measured to 0.01 mm with a digital caliper. Pearson correlation and T-test were used for the statistical analysis. RESULTS/STATISTICS: The combination of the sums of the four lower incisors and the first upper molars showed the best prediction capability for the SPCP in the Italian sample. Moreover new regression equations were formulated including sex and arch as additional predictor variables. In 80% of the cases estimated differences between the predicted and the actual values were smaller than 1 mm. CONCLUSION: It can be concluded that the new regression equations proposed seemed to show good accuracy.

Management of unilateral condylar fracture in a 9.6-year-old female.

BACKGROUND: Fractures represent a particular kind of pathology in children, as they take place within a rapidly growing organism. Condylar fractures must be focused upon not only as a cause of direct damage to the bone structure, but also with regards to future disorders in the dentofacial development, skeletal deformities and articular dysfunctions. The treatment aims at restoring function, occlusion, and symmetry. Aim of this paper is to emphasise, through the description of a case report, the need for correct diagnosis and the importance of a functional treatment by means of early muscle activation, in order to prevent any consequences on facial development. CASE REPORT: A case of a 9.6-year-old female with monocondylar and intracapsular fracture following a car accident is described. In accordance with the literature, the patient did not undergo surgical treatment, but followed a functional orthodontic protocol. The significant symptoms reduction and the rapid improvement of mandibular functions confirm the excellent healing potential in paediatric age, while the X-ray evaluations 1 year and 3.7 years later testify the condylar reshaping. Since the latter can continue over many years, the clinical and radiological follow-ups of the patient will have to cover the entire growth period.

Grafting derivatives of Mn6 single-molecule magnets with high anisotropy energy barrier on Au111 surface.

We study the magnetic properties of two new functionalized single-molecule magnets belonging to the Mn 6 family (general formula [Mn (III)6O2(R-sao)6(O2C-th)2L(4-6)], where R=H (1) or Et (2), HO2C-th=3-thiophene carboxylic acid, L=EtOH, H2O and saoH2 is salicylaldoxime) and their grafting on the Au(111) surface. Complex 1 exhibits spin ground-state S=4, as the result of ferromagnetic coupling between the two antiferromagnetic Mn (III) 3 triangles, while slight structural changes in complex 2, switch the dominant magnetic exchange interactions from anti- to ferromagnetic, enhancing the spin ground-state to S=12 and, consequently, the effective energy barrier for the relaxation of magnetization. Direct-current and alternating-current magnetic susceptibility measurements show that the functionalized complexes preserve the main magnetic properties of the corresponding not-functionalized Mn 6 clusters (i.e., total spin value and magnetic behavior as a function of temperature), though a reduction of the anisotropy barrier is observed in complex 2. For both complexes, the -O2C-th functionalization allows the direct grafting on Au(111) surface by liquid-phase deposition. X-ray photoemission spectroscopy demonstrates that the stoichiometry of the molecular cores is preserved after grafting. Scanning tunneling microscopy (STM) reveals a sub-monolayer distribution of isolated clusters with a slightly higher coverage for complex 1. The cluster stability in the STM images and the S-2p energy positions demonstrate, for both derivatives, the strength of the grafting with the gold surface.

Probing magnetic coupling between LnPc2 (Ln = Tb, Er) molecules and the graphene/Ni (111) substrate with and without Au-intercalation: role of the dipolar field.

Lanthanides (Ln) bis-phthalocyanine (Pc), the so-called LnPc2double decker, are a promising class of molecules with a well-defined magnetic anisotropy. In this work, we investigate the magnetic properties of LnPc2 molecules UHV-deposited on a graphene/Ni(111) substrate and how they modify when an Au layer is intercalated between Ni and graphene. X-ray absorption spectroscopy (XAS), and linear and magnetic circular dichroism (XLD and XMCD) were used to characterize the systems and probe the magnetic coupling between LnPc2 molecules and the Ni substrate through graphene, both gold-intercalated and not. Two types of LnPc2 molecules (Ln = Tb, Er) with a different magnetic anisotropy (easy-axis for Tb, easy-plane for Er) were considered. XMCD shows an antiferromagnetic coupling between Ln and Ni(111) even in the presence of the graphene interlayer. Au intercalation causes the vanishing of the interaction between Tb and Ni(111). In contrast, in the case of ErPc2, we found that the gold intercalation does not perturb the magnetic coupling. These results, combined with the magnetic anisotropy of the systems, suggest the possible importance of the magnetic dipolar field contribution for determining the magnetic behaviour.

CD133+ brain tumor-initiating cells are dependent on STAT3 signaling to drive medulloblastoma recurrence.

Medulloblastoma (MB), the most common malignant paediatric brain tumor, is currently treated using a combination of surgery, craniospinal radiotherapy and chemotherapy. Owing to MB stem cells (MBSCs), a subset of MB patients remains untreatable despite standard therapy. CD133 is used to identify MBSCs although its functional role in tumorigenesis has yet to be determined. In this work, we showed enrichment of CD133 in Group 3 MB is associated with increased rate of metastasis and poor clinical outcome. The signal transducers and activators of transcription-3 (STAT3) pathway are selectively activated in CD133+ MBSCs and promote tumorigenesis through regulation of c-MYC, a key genetic driver of Group 3 MB. We screened compound libraries for STAT3 inhibitors and treatment with the selected STAT3 inhibitors resulted in tumor size reduction in vivo. We propose that inhibition of STAT3 signaling in MBSCs may represent a potential therapeutic strategy to treat patients with recurrent MB.