Late-forming supernumerary teeth: A case series.

The aim of this case series was to illustrate the development of late-forming supernumerary teeth (LFST) and highlight the implications for orthodontic treatment. There are limited studies relating to the aetiology, prevalence and treatment of LFST and the cases presented here demonstrate the management of LFST within a tertiary care centre. Five cases are presented, which show various presentations and chronological ages in the development of LFST. This case series emphasises the significance of maintaining a low threshold for suspecting LFST in patients where supernumerary teeth have previously been identified. It also highlights the importance of regular clinical and radiographic reviews. Timely identification can help prevent complications and optimise treatment outcomes.

A Clinical Decision Tool for Risk Stratifying Patients with Systemic Sclerosis-Related Pulmonary Hypertension.

We devised a scoring system to identify patients with systemic sclerosis (SSc) at risk for pulmonary hypertension (PH) and predict all-cause mortality. Using 7 variables obtained via pulmonary function testing, echocardiography, and computed tomographic chest imaging, we applied the score to a retrospective cohort of 117 patients with SSc. There were 60 (51.3%) who were diagnosed with PH by right heart catheterization. Using a scoring threshold ≥ 0, our decision tool predicted PH with a sensitivity, specificity, and accuracy of 0.87 (95% CI 0.75, 0.94), 0.74 (95% CI 0.60, 0.84), and 0.80 (95% CI 0.72, 0.87), respectively. When adjusted for age at PH diagnosis, sex, and receipt of pulmonary arterial vasodilators, each one-point score increase was associated with an adjusted HR of 1.19 (95% CI 1.05, 1.34) for all-cause mortality. With further validation in external cohorts, our simplified clinical decision tool may better streamline earlier detection of PH in SSc.

Protein Tyrosine Phosphatase Non-Receptor 11 (PTPN11/Shp2) as a Driver Oncogene and a Novel Therapeutic Target in Non-Small Cell Lung Cancer (NSCLC).

PTPN11 encodes the SHP2 protein tyrosine phosphatase that activates the mitogen-activated protein kinase (MAPK) pathway upstream of KRAS and MEK. PTPN11/Shp2 somatic mutations occur frequently in Juvenile myelomonocytic leukaemia (JMML); however, the role of mutated PTPN11 in lung cancer tumourigenesis and its utility as a therapeutic target has not been fully addressed. We applied mass-spectrometry-based genotyping to DNA extracted from the tumour and matched the normal tissue of 356 NSCLC patients (98 adenocarcinomas (LUAD) and 258 squamous cell carcinomas (LUSC)). Further, PTPN11 mutation cases were identified in additional cohorts, including TCGA, Broad, and MD Anderson datasets and the COSMIC database. PTPN11 constructs harbouring PTPN11 E76A, A72D and C459S mutations were stably expressed in IL-3 dependent BaF3 cells and NSCLC cell lines (NCI-H1703, NCI-H157, NCI-H1299). The MAPK and PI3K pathway activation was evaluated using Western blotting. PTPN11/Shp2 phosphatase activity was measured in whole-cell protein lysates using an Shp2 assay kit. The Shp2 inhibitor (SHPi) was assessed both in vitro and in vivo in a PTPN11-mutated cell line for improved responses to MAPK and PI3K targeting therapies. Somatic PTPN11 hotspot mutations occurred in 4/98 (4.1%) adenocarcinomas and 7/258 (2.7%) squamous cells of 356 NSCLC patients. Additional 26 PTPN11 hotspot mutations occurred in 23 and 3 adenocarcinomas and squamous cell carcinoma, respectively, across the additional cohorts. Mutant PTPN11 significantly increased the IL-3 independent survival of Ba/F3 cells compared to wildtype PTPN11 (p < 0.0001). Ba/F3, NCI-H1703, and NCI-H157 cells expressing mutant PTPN11 exhibited increased PTPN11/Shp2 phosphatase activity and phospho-ERK1/2 levels compared to cells expressing wildtype PTPN11. The transduction of the PTPN11 inactivating mutation C459S into NSCLC cell lines led to decreased phospho-ERK, as well as decreased phospho-AKT in the PTPN11-mutated NCI-H661 cell line. NCI-H661 cells (PTPN11-mutated, KRAS-wild type) were significantly more sensitive to growth inhibition by the PI3K inhibitor copanlisib (IC50: 13.9 ± 4.7 nM) compared to NCI-H1703 (PTPN11/KRAS-wild type) cells (IC50: >10,000 nM). The SHP2 inhibitor, in combination with the PI3K targeting therapy copanlisib, showed no significant difference in tumour development in vivo; however, this significantly prevented MAPK pathway induction in vitro (p < 0.0001). PTPN11/Shp2 demonstrated the in vitro features of a driver oncogene and could potentially sensitize NSCLC cells to PI3K inhibition and inhibit MAPK pathway activation following PI3K pathway targeting.

Orthodontic apps: An assessment of content accuracy and validity.

OBJECTIVE: To assess the content accuracy of orthodontic treatment information in patient-focused apps. DESIGN: A cross-sectional review study. SETTING: Orthodontic apps available on the UK Android and Apple App Stores. METHODS: Apps identified in a previous research study and those identified via a questionnaire of specialist orthodontists were assessed for accuracy of content utilising an evidence-based checklist. The checklist covered five main orthodontically relevant themes and 32 codes with respective items. RESULTS: The accuracy of information content for 16 patient-focused apps was assessed. Eight apps provided information related to orthodontic treatment and handling emergencies. Five apps were reminder apps and a small number (n = 3) contained games and timers for toothbrushing and aligners. With regard to the accuracy of information content, only two apps contained information across all five themes of the evidence-based checklist. Only one app received a score of 'fair - excellent' under the oral hygiene theme; interestingly, this app was the most commonly used patient-focused app. Eight apps containing orthodontic treatment information scored poorly as they had inaccurate information on handling emergency situations. None of the apps were deemed excellent with regard to accuracy of information content. CONCLUSION: The orthodontic mobile apps assessed in this study mostly contained information of poor accuracy. Therefore, there is a need for high-quality apps with credible information supported by evidence to be developed.

The awareness and usage of orthodontic apps and social media by orthodontists in the UK: A questionnaire-based study.

OBJECTIVE: To assess the awareness and usage of mobile apps and social media among orthodontic clinicians to support patients with orthodontic treatment, support the professional development of orthodontists, and identify any relevant apps and social media platforms currently recommended to patients. DESIGN: Cross-sectional questionnaire-based study. SETTING: United Kingdom. METHODS: A questionnaire was developed and distributed to members of the British Orthodontic Society (BOS). To increase the response rate, the questionnaire was circulated at three time points between January and March 2020. RESULTS: A total of 149 orthodontists responded to the questionnaire (15% response rate) with 113 orthodontists completing all questions (11.4%). Of those who answered, 81% (n = 111) had been qualified for >10 years, 35% worked in practice (n = 48), 34% worked in a hospital (n = 47) and 26% worked in both hospital and practice (n = 36). The results indicated that 20% of clinicians (n = 22) used apps to support patients and 33% (n = 37) reported using apps for professional purposes. Brush DJ appeared to be the most popular patient focused app (39%, n = 18) whereas the IOTN (17%, n = 8), Invisalign (17%, n = 8) and Dental Monitoring apps (9%, n = 4) were the most popular clinician-focused apps. With regard to social media, 53% (n = 60) of respondents reported that they used social media to communicate generic orthodontic information and promote their practice to patients. The most commonly used social media platforms were Facebook and Instagram. Of respondents, 96% expressed a willingness to recommend an evidence-based mobile app to patients if available, and 88% were willing to recommend an evidence-based social media platform. CONCLUSIONS: Orthodontic clinicians are utilising mobile apps and social media to support both patients and their own professional development. There is a willingness to increase the use of evidence-based platforms and apps to support patients.

Reduced cardiomyocyte Na+ current in the age-dependent murine Pgc-1ß-/- model of ventricular arrhythmia.

Peroxisome proliferator-activated receptor-γ coactivator-1 deficient (Pgc-1ß-/- ) murine hearts model the increased, age-dependent, ventricular arrhythmic risks attributed to clinical conditions associated with mitochondrial energetic dysfunction. These were accompanied by compromised action potential (AP) upstroke rates and impaired conduction velocities potentially producing arrhythmic substrate. We tested a hypothesis implicating compromised Na+ current in these electrophysiological phenotypes by applying loose patch-clamp techniques in intact young and aged, wild-type (WT) and Pgc-1ß-/- , ventricular cardiomyocyte preparations for the first time. This allowed conservation of their in vivo extracellular and intracellular conditions. Depolarising steps elicited typical voltage-dependent activating and inactivating inward Na+ currents with peak amplitudes increasing or decreasing with their respective activating or preceding inactivating voltage steps. Two-way analysis of variance associated Pgc-1ß-/- genotype with independent reductions in maximum peak ventricular Na+ currents from -36.63 ± 2.14 (n = 20) and -35.43 ± 1.96 (n = 18; young and aged WT, respectively), to -29.06 ± 1.65 (n = 23) and -27.93 ± 1.63 (n = 20; young and aged Pgc-1ß-/- , respectively) pA/µm2 (p < 0.0001), without independent effects of, or interactions with age. Voltages at half-maximal current V*, and steepness factors k in plots of voltage dependences of both Na+ current activation and inactivation, and time constants for its postrepolarisation recovery from inactivation, remained indistinguishable through all experimental groups. So were the activation and rectification properties of delayed outward (K+ ) currents, demonstrated from tail currents reflecting current recoveries from respective varying or constant voltage steps. These current-voltage properties directly implicate decreases specifically in maximum available Na+ current with unchanged voltage dependences and unaltered K+ current properties, in proarrhythmic reductions in AP conduction velocity in Pgc-1ß-/- ventricles.

Is visual imagery ability higher for orthodontic students than those in other disciplines? A cross-sectional questionnaire-based study.

OBJECTIVE: To investigate the effect visual imagery may have on career choice among current university students across a range of subjects and disciplines. SETTING: University College London (UCL), UK. DESIGN: Cross-sectional questionnaire-based study. PARTICIPANTS: The study compared four main groups of UCL students: current students at the Slade School of Fine Art; UCL Eastman Dental Institute; UCL Bartlett School of Architecture; and the Faculty of Laws. METHOD: A questionnaire based on the Vividness of Visual Imagery Questionnaire (VVIQ) was distributed along with questions regarding demographic information. RESULTS: There were no significant differences between the VVIQ scores across the four included Schools/Faculty: The Slade School of Fine Art; UCL Bartlett School of Architecture; Faculty of Laws; and UCL Eastman Dental Institute, F(3,219) = 2.160, P = 0.094. There were also no significant differences in the scores for the Eastman (M = 60.21, SD = 13.58) and the three other Schools/Faculty (M = 62.87, SD = 10.96); t(-1.317) = 221, P = 0.189, and no significant difference in the scores for the Orthodontic students (M = 60.80, SD = 13.39) and the remaining other included students (M = 61.44, SD = 9.68); t(-0.232) = 221, P = 0.817. Aphantasia was uncommon in this sample, with a prevalence of 0.9%. A positive correlation was found between age group and total VVIQ score, with older participants scoring higher on the VVIQ. Women were significantly more likely to say that their ability to visualise had affected their career choice than male respondents. CONCLUSIONS: There were no significant differences between the VVIQ scores across the four included Schools/Faculty. Visual imagery ability did not differ in dental or orthodontic students in comparison to other student groups. Further work is needed to replicate these findings in more diverse samples.

Preventing white spot lesions with fluoride pastes.

Design Randomised controlled trial.Study population Patients undergoing routine orthodontic treatment, aged 12 years and older, were randomly allocated to use either Clinpro 5000, Clinpro Tooth Crème or MI Paste Plus for 4 months.Data Analysis Three-way analysis of variance (ANOVA) was used to analyse the Enamel Decalcification Index (EDI) scores of the maxillary and mandibular arches from the right first premolar to the left first premolar at 0.05 level of significance. Fisher-protected least significant difference intervals were used to compare mean EDI scores. Two operators scored photographs independently and their scores were compared by using the t-test; no statistically significant difference (P ≥.05) was found between the operators. Results of each product were analysed individually and amongst themselves. A multilevel mixed-effects Poisson regression was used to model factors predictive of EDI scores for individual teeth.Results Of the 120 subjects enrolled, 100 (35 using Clinpro 5000, 32 using Clinpro Tooth Crème, and 33 using MI Paste Plus) completed the study. The data lends support for Clinpro 5000 providing superior protection against enamel decalcification when compared to Clinpro Crème, and mixed support when compared to MI Paste Plus.Conclusions The use of Clinpro 5000, Clinpro Tooth Crème, and MI Paste Plus all have a reduction effect on white spot lesions when compared to studies reported previously. They found Clinpro 5000 to have a marginally better effect than the two other test pastes.

Early treatment of class III malocclusion with facemask.

Data sourcesThe Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase, Medline and the ClinicalTrials.gov databases.Study selectionRandomised controlled trials (RCTs) and controlled clinical trials (CCTs) of children aged 7-12 years with class III malocclusion undergoing fixed or removable orthodontic treatment for early correction were included.Data extraction and synthesisTwo reviewers independently selected studies, abstracted data and assessed risk of bias. The Cochrane risk of bias tool was used for RCTs and the Downs and Black and the Newcastle-Ottawa scales for CCTs. The primary outcome was correction of reverse overjet. Mean differences (MD) with 95% confidence intervals were calculated and a random effects meta-analysis conducted.ResultsFifteen studies (nine RCTs, six CCTs) were included. Only three of the RCTs were considered to be at low risk of bias, all six CCTs were at high risk of bias.Three RCTs (141 patients) compared protraction facemask and untreated control. The results for reverse overjet (MD = 2.5 mm; 95% CI, 1.21-3.79) and ANB angle (MD = 3.90˚; 95% CI, 3.54-4.25) were statistically significant favouring the facemask group. All CCTs demonstrated a statistically significant benefit in favour of the use of each appliance. However, the studies had high risk of bias.ConclusionsThere is a moderate amount of evidence to show that early treatment with a facemask results in positive improvement for both skeletal and dental effects in the short term. However, there was lack of evidence on long-term benefits. There is some evidence with regard to the chincup, tandem traction bow appliance and removable mandibular retractor, but the studies had a high risk of bias. Further high-quality, long-term studies are required to evaluate the early treatment effects for Class III malocclusion patients.

A Multimodal Prediction Model for Diagnosing Pulmonary Hypertension in Systemic Sclerosis.

OBJECTIVE: Diagnosis of pulmonary hypertension (PH) in systemic sclerosis (SSc) requires an invasive right heart catheterization (RHC), often based on an elevated estimated pulmonary artery systolic pressure on screening echocardiography. However, because of the poor specificity of echocardiography, a greater number of patients undergo RHC than necessary, exposing patients to potentially avoidable complication risks. The development of improved prediction models for PH in SSc may inform decision-making for RHC in these patients. METHODS: We conducted a retrospective study of 130 patients with SSc; 66 (50.8%) were diagnosed with PH by RHC. We used data from pulmonary function testing, electrocardiography, echocardiography, and computed tomography to identify and compare the performance characteristics of 3 models predicting the presence of PH: 1) random forest, 2) classification and regression tree, and 3) logistic regression. For each model, we generated receiver operating curves and calculated sensitivity and specificity. We internally validated models using a train-test split of the data. RESULTS: The random forest model performed best with an area under the curve of 0.92 (95% confidence interval [95% CI] 0.83-1.00), sensitivity of 0.95 (95% CI 0.75-1.00), and specificity of 0.80 (95% CI 0.56-0.94). The 2 most important variables in our random forest model were pulmonary artery diameter on chest computed tomography and diffusing capacity for carbon monoxide on pulmonary function testing. CONCLUSIONS: In patients with SSc, a random forest model can aid in the detection of PH with high sensitivity and specificity and may allow for better patient selection for RHC, thereby minimizing patient risk.

Evidence for a mixed-age group in a pterosaur footprint assemblage from the early Upper Cretaceous of Korea.

Here we describe a new pterosaur footprint assemblage from the Hwasun Seoyuri tracksite in the Upper Cretaceous Jangdong Formation of the Neungju Basin in Korea. The assemblage consists of many randomly oriented prints in remarkably high densities but represents a single ichnotaxon, Pteraichnus. Individuals exhibit a large but continuous size range, some of which, with a wingspan estimated at 0.5 m, are among the smallest pterosaurs yet reported from the Upper Cretaceous, adding to other recent finds which contradict the idea that large and giant forms entirely dominated this interval. Unusual features of the tracks, including relatively long, slender pedal digit impressions, do not match the pes of any known Cretaceous pterosaur, suggesting that the trackmakers are as yet unknown from the body fossil record. The Hwasun pterosaur footprints appear to record gregarious behavior at the exact location by individuals of different ages, hinting at the possibility that pterosaurs gathered in mixed-age groups.

Exhaled Breath Condensate (EBC) analysis of circulating tumour DNA (ctDNA) using a lung cancer specific UltraSEEK oncogene panel.

INTRODUCTION: Small diagnostic tissue samples can be inadequate in testing an expanding list of validated oncogenic driver alterations and fail to reflect intratumour heterogeneity (ITGH) in lung cancer. Liquid biopsies are non-invasive and may better reflect ITGH. Most liquid biopsies are performed in the context of circulating tumour DNA (ctDNA) in plasma but Exhaled Breath Condensate (EBC) shows promise as a lung-specific liquid biopsy. METHODS: In this prospective, proof-of-concept study we carried out targeted Next Generation Sequencing (NGS) on diagnostic tissue samples from 125 patients with lung cancer and compared results to plasma and EBC for 5 oncogenic driver mutations (EGFR, KRAS, PIK3CA, ERBB2, BRAF) using an ultrasensitive PCR technique (UltraSEEK™ Lung Panel on the MassARRAY® System, Agena Bioscience, San Diego, CA, USA). RESULTS: There was a significantly higher failure rate due to unamplifiable DNA in tissue NGS (57/125, 45.6%) compared to plasma (27/125, 21.6%, p < 0.001 and EBC (26/125,20.8%, p ≤ 0.001. Consequently, both plasma and EBC identified higher number of mutations compared to tissue NGS. Specifically, there were significantly higher numbers of mutations detected in EGFR, KRAS and PIK3CA in plasma (p = 9.82 × 10-3, p = 3.14 × 10-5, p = 1.95 × 10-3) and EBC (p = 2.18 × 10-3, p = 2.28 × 10-4,p = 0.016) compared to tissue NGS. There was considerable divergence in mutation profiles between plasma and EBC with 34/76 (44%) mutations detected in plasma and 37/74 (41.89%) in EBC unique to their respective liquid biopsy. CONCLUSIONS: The results suggest that EBC is effective in identifying clinically relevant alterations in patients with lung cancer using UltraSEEK™ and has a potential role as an adjunct to plasma testing.

High- versus Low-Spin Ni2+ in Elongated Octahedral Environments: Sr2NiO2Cu2Se2, Sr2NiO2Cu2S2, and Sr2NiO2Cu2(Se1-x S x )2.

Sr2NiO2Cu2Se2, comprising alternating [Sr2NiO2]2+ and [Cu2Se2]2- layers, is reported. Powder neutron diffraction shows that the Ni2+ ions, which are in a highly elongated NiO4Se2 environment with D4h symmetry, adopt a high-spin configuration and carry localized magnetic moments which order antiferromagnetically below ∼160 K in a √2a × âˆš2a × 2c expansion of the nuclear cell with an ordered moment of 1.31(2) µB per Ni2+ ion. The adoption of the high-spin configuration for this d 8 cation in a pseudo-square-planar ligand field is supported by consideration of the experimental bond lengths and the results of density functional theory (DFT) calculations. This is in contrast to the sulfide analogue Sr2NiO2Cu2S2, which, according to both experiment and DFT calculations, has a much more elongated ligand field, more consistent with the low-spin configuration commonly found for square-planar Ni2+, and accordingly, there is no evidence for magnetic moment on the Ni2+ ions. Examination of the solid solution Sr2NiO2Cu2(Se1-x S x )2 shows direct evidence from the evolution of the crystal structure and the magnetic ordering for the transition from high-spin selenide-rich compounds to low-spin sulfide-rich compounds as a function of composition. Compression of Sr2NiO2Cu2Se2 up to 7.2 GPa does not show any structural signature of a change in the spin state. Consideration of the experimental and computed Ni2+ coordination environments and their subtle changes as a function of temperature, in addition to transitions evident in the transport properties and magnetic susceptibilities in the end members, Sr2NiO2Cu2Se2 and Sr2NiO2Cu2S2, suggest that simple high-spin and low-spin models for Ni2+ may not be entirely appropriate and point to further complexities in these compounds.

Primary pulmonary marginal zone lymphoma: an unusual cause of pulmonary infiltrates.

Primary pulmonary extra-nodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), also known as bronchus-associated lymphoid tissue (BALT lymphoma), is the most common primary pulmonary lymphoma but is rare (<1%) among all non-Hodgkin lymphomas and among pulmonary neoplasms in general. We herein report the case of a 59-year-old male who presented with stable exertional dyspnoea and persistent lung infiltrates who was referred to our hospital for further assessment. A computed tomography (CT)-guided core biopsy was performed showing a dense lymphoid infiltrate, with further testing revealing the diagnosis of pulmonary MALT lymphoma. This uncommon lung tumour is usually seen in older adults and typically associated with a relatively indolent course. Rituximab, an anti-CD20 antibody, has been shown to be effective in up to 70% of cases.