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BACKGROUND: The MInT study was the first to show improved 3-year outcomes with the addition of rituximab to a CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-like regimen in young patients with good-prognosis diffuse large-B-cell lymphoma. Extended follow-up was needed to establish long-term effects. METHODS: In the randomised open-label MInT study, patients from 18 countries (aged 18-60 years with none or one risk factor according to the age-adjusted International Prognostic Index [IPI], stage II-IV disease or stage I disease with bulk) were randomly assigned to receive six cycles of a CHOP-like chemotherapy with or without rituximab. Bulky and extranodal sites received additional radiotherapy. Randomisation was done centrally with a computer-based tool and was stratified by centre, bulky disease, age-adjusted IPI, and chemotherapy regimen by use of a modified minimisation algorithm that incorporated a stochastic component. Patients and investigators were not masked to treatment allocation. The primary endpoint was event-free survival. Analyses were by intention to treat. This observational study is a follow-up of the MInT trial, which was stopped in 2003, and is registered at ClinicalTrials.gov, number NCT00400907. FINDINGS: The intention-to-treat population included 410 patients assigned to chemotherapy alone and 413 assigned to chemotherapy plus rituximab. After a median follow-up of 72 months (range 0·03-119), 6-year event-free survival was 55·8% (95% CI 50·4-60·9; 166 events) for patients assigned to chemotherapy alone and 74·3% (69·3-78·6; 98 events) for those assigned to chemotherapy plus rituximab (difference between groups 18·5%, 11·5-25·4, log-rank p<0·0001). Multivariable analyses showed that event-free survival was affected by treatment group, presence of bulky disease, and age-adjusted IPI and that overall survival was affected by treatment group and presence of bulky disease only. After chemotherapy and rituximab, a favourable subgroup (IPI=0, no bulk) could be defined from a less favourable subgroup (IPI=1 or bulk, or both; event-free survival 84·3% [95% CI 74·2-90·7] vs 71·0% [65·1-76·1], log-rank p=0·005). 18 (4·4%, 95% CI 2·6-6·9) second malignancies occurred in the chemotherapy-alone group and 16 (3·9%, 2·2-6·2) in the chemotherapy and rituximab group (Fisher's exact p=0·730). INTERPRETATION: Rituximab added to six cycles of CHOP-like chemotherapy improved long-term outcomes for young patients with good-prognosis diffuse large-B-cell lymphoma. The definition of two prognostic subgroups allows a more refined therapeutic approach to these patients than does assessment by IPI alone. FUNDING: Hoffmann-La Roche. [ABSTRACT FROM AUTHOR]

Pathological tooth wear is a dental problem that affects all age groups and appears to be increasing in prevalence. A subset of these patients may benefit from a combination of orthodontic and restorative care which will be discussed in this article. Orthodontics can help to create the necessary vertical, anterior-posterior and mesio-distal space for restorative work, reducing the need for tooth reduction and lessening the biological costs of restorative care, helping to reposition the gingival margins where this impacts upon aesthetics, as well as correcting co-existing malocclusion., (© 2024. The Author(s), under exclusive licence to the British Dental Association.)

Cancer has been a significant threat to human health and well-being, posing the biggest obstacle in the history of human sickness. The high death rate in cancer patients is primarily due to the complexity of the disease and the wide range of clinical outcomes. Increasing the accuracy of the prediction is equally crucial as predicting the survival rate of cancer patients, which has become a key issue of cancer research. Many models have been suggested at the moment. However, most of them simply use single genetic data or clinical data to construct prediction models for cancer survival. There is a lot of emphasis in present survival studies on determining whether or not a patient will survive five years. The personal issue of how long a lung cancer patient will survive remains unanswered. The proposed technique Naive Bayes and SSA is estimating the overall survival time with lung cancer. Two machine learning challenges are derived from a single customized query. To begin with, determining whether a patient will survive for more than five years is a simple binary question. The second step is to develop a five-year survival model using regression analysis. When asked to forecast how long a lung cancer patient would survive within five years, the mean absolute error (MAE) of this technique's predictions is accurate within a month. Several biomarker genes have been associated with lung cancers. The accuracy, recall, and precision achieved from this algorithm are 98.78%, 98.4%, and 98.6%, respectively., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Sonia Kukreja et al.)

Objectives: To investigate the relationship between self-reported self-harm and dislike of dentofacial features and oral health-related quality of life (OHRQoL)., Materials and Methods: Anonymous, self-reporting questionnaires were completed by 699 school children (aged 13-14 years), representing over 1% of the age group in Amman, Jordan. Participants were invited from 23 randomly selected schools in 10 educational directorates. OHRQoL was assessed using the Child Perception Questionnaire (CPQ 11-14). Self-harm was assessed using a constructed self-reporting questionnaire. The relationship between OHRQoL and self-harm was assessed and significant findings were identified at probability of α = 0.05., Results: Over one-quarter of schoolchildren (26.9%, n = 88) admitted self-harming behavior. Self-harm was reported to be due to dislike of dentofacial appearance among 12.9% of participants (n = 90). Higher CPQ 11-14 total scores and individual dimension scores were associated with the presence of self-harm (P < .001). High self-harm incidence was reported among participants who had dentofacial features that affected appearance (P < .001). Among subjects admitting self-harm, the frequency of self-harming behavior ranged from once to over 10 times per year., Conclusions: Significant relationships were found between self-harm and dislike of dentofacial features and OHRQoL., (© 2022 by The EH Angle Education and Research Foundation, Inc.)

Introduction: Children with Apert syndrome have hypertelorism and midfacial hypoplasia, which can be treated with facial bipartition (FB), often aided by rigid external distraction. The technique involves a midline osteotomy that lateralizes the maxillary segments, resulting in posterior cross-bites and midline diastema. Varying degrees of spontaneous realignment of the dental arches occurs postoperatively. This study aims to quantify these movements and assess whether they occur as part of a wider skeletal relapse or as dental compensation., Methods: Patients who underwent FB and had high quality computed tomography scans at the preoperative stage, immediately postsurgery, and later postoperatively were reviewed. DICOM files were converted to three-dimensional bone meshes and anatomical point-to-point displacements were quantified using nonrigid iterative closest point registration. Displacements were visualized using arrow maps, thereby providing an overview of the movements of the facial skeleton and dentition., Results: Five patients with Apert syndrome were included. In all cases, the arrow maps demonstrated initial significant anterior movement of the frontofacial segment coupled with medial rotation of the orbits and transverse divergence of the maxillary arches. The bony position following initial surgery was shown to be largely stable, with primary dentoalveolar relapse correcting the dental alignment., Conclusions: This study showed that spontaneous dental compensation occurs following FB without compromising the surgical result. It may be appropriate to delay active orthodontic for 6-months postoperatively until completion of this early compensatory phase., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by Mutaz B. Habal, MD.)

Background: To test the hypothesis that in profile smiling view, for ideal aesthetics, a tangent to the labial face of the maxillary central incisor crowns should be approximately parallel to the true vertical line and thereby perpendicular to the true horizontal line., Methods: An idealized female image was created with computer software and manipulated using the same software to construct an "ideal" female profile image with proportions, and linear and angular soft tissue measurements, based on currently accepted criteria for idealized Caucasian profiles. The maxillary incisor labial face tangent was altered in 5° increments from 70 to 120°, creating a range of images, shown in random order to 70 observers (56 lay people and 14 clinicians), who ranked the images from the most to the least attractive. The main outcome was the preference ranks of image attractiveness given by the observers., Results: The most attractive inclination of a tangent to the labial face of the maxillary incisor crowns in profile view in relation to the true horizontal line was 85°, i.e. 5° retroclined from a perpendicular 90° inclination. The most attractive range appears to be between 80 and 90°. Excessive proclination appeared to be less desirable than retroclination. Beyond 105° most observers recommend treatment., Conclusion: In natural head position, the ideal inclination of the maxillary incisor crown labial face tangent in profile view will be approximately parallel to the true vertical line and thereby approximately perpendicular to the true horizontal line., Competing Interests: Competing interestsThe authors declare that they have no competing interests.

Here, we provide a brief overview of the challenges, innovations and potential opportunities facing contemporary management of individuals requiring orthognathic care.

Facial feminisation surgery (FFS) aims to feminise the face by changing masculine facial features to feminine ones. It is commonly undertaken for transsexual individuals who are transitioning from male to female or for women who wish to further feminise their facial appearance. Assessment and treatment planning by a multidisciplinary team is essential for any patient considering FFS. Orthodontists have an important role within this team as patients may first present to an orthodontist expressing concerns about the appearance of their jaws. Therefore, it is important that orthodontists have a detailed understanding of FFS procedures, to enable good patient communication, thorough patient assessment and onwards referral where required. This article reviews the common FFS procedures, their indications, and the benefits and risks of each procedure and highlights the role of the orthodontist.

Background: Treatment planning the correction of a transverse maxillary occlusal plane cant often involves a degree of qualitative "eyeballing", with the attendant possibility of error in the estimated judgement. A simple chair side technique permits quantification of the extent of asymmetry and thereby quantitative measurements for the correction of the occlusal plane cant., Methods: A measuring instrument may be constructed by soldering the edge of a stainless steel dental ruler at 90° to the flat surface of a similar ruler. With the patient either standing in natural head position, or alternatively seated upright in the dental chair, and a dental photographic retractor in situ, the flat under-surface of the horizontal part of this measuring instrument is placed on a unilateral segment of a bilateral structure, e.g. the higher maxillary canine orthodontic bracket hook. The vertical ruler is held next to the contralateral canine tooth, and the vertical distance measured directly from the canine bracket to the flat under-surface of the horizontal part of the measuring instrument., Results: This vertical distance quantifies the overall extent of movement required to level the maxillary occlusal plane., Conclusions: This measuring instrument and simple chair side technique helps to quantify the overall extent of surgical levelling required and may be a useful additional technique in our clinical diagnostic armamentarium., Competing Interests: Ethical approval was not required.The subject in Figs. 2 and 3 provided written consent for his images to be published.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Patients presenting with severe hypodontia can be challenging to manage. They often present with significant spaces within the dental arches and the lack of permanent teeth can make anchorage control difficult. This case report demonstrates a novel technique for diastema closure in a 14-year-old with severe hypodontia. The technique allows maintenance of root parallelism during space closure in cases with reduced anchorage support. The treatment plan was agreed on a multidisciplinary hypodontia clinic and involved an upper sectional fixed orthodontic appliance to close a 7-mm midline diastema aiding subsequent partial denture provision. Treatment commenced by bonding upper primary canines and central incisors. However, attempting space closure on a 0.019 × 0.025-inch stainless-steel working archwire resulted in tipping of the incisor crowns. Two brackets were therefore placed on the labial surface of each central incisor (one incisal and one gingival). Subsequently two stainless steel working archwires and elastomeric chain were used for diastema closure. This four-bracket system provided superior control allowing space closure by bodily tooth movement. Excellent root parallelism was achieved with this innovative technique.

Background The objective of the study was to evaluate the long-term outcome of paediatric-onset hyperthyroidism with follow-up into adulthood and to identify any early predictors of a need for definitive therapy (DT). Methods In a retrospective analysis of patients diagnosed with hyperthyroidism under the age of 18 years and at follow-up, a comparison was made by categorising them into those who underwent definitive therapy (DT group), i.e. thyroidectomy/radioactive iodine (RAI), those who remained on antithyroid drugs (ATD) (CBZ group) and those who had complete remission (RE group). Results Sixty-one (49 females, 12 males) patients with a median age of 15.1 years (range: 3.6-18) at diagnosis were studied. The duration of the first course of ATD varied from <1 year (7%), 1-2 years (26%), >2 years (46%) and ATD never discontinued (21%). Disease relapsed in 69% of patients with <1 year of ATD vs. 79% with >2 years of ATD. At follow-up, the median duration since diagnosis was 8.75 years (range 2.0-20.7 years) and the median age at follow-up was 23.2 years (8-36 years). Thirty-three percent (20/61) had undergone DT (DT group) - with 16.5% (n=10) on RAI and 16.5% (n=10) on surgery, 36% (22/61) were on ATD (CBZ group), whilst 32% (19/61) had undergone full remission (RE group). The comparison did not identify any statistically significant difference for predictor factors at diagnosis including age, T4 and free T4 levels, thyroid peroxidise antibody levels (TPO) and the duration of the first course of carbimazole (CBZ) treatment. Conclusion Long-term complete remission of paediatric-onset hyperthyroidism in our study was 31%. There were no predictors identified that could help predict the long-term outcome, especially into adulthood.

Chemoimmunotherapy (CIT) and targeted therapy with single-agent ibrutinib are both recommended first-line treatments for chronic lymphocytic leukemia (CLL), although their outcomes have not been directly compared. Using ibrutinib data from the RESONATE-2 (PCYC-1115/1116) study conducted in patients ≥65 years without del(17p), we performed a cross-trial comparison with CIT data from published phase 3 studies in first-line treatment of CLL. Progression-free survival (PFS), overall survival (OS), and safety data for ibrutinib (median follow-up 35.7 months) were evaluated alongside available CIT data. CIT regimens included: fludarabine + cyclophosphamide + rituximab (CLL8, CLL10), bendamustine + rituximab (CLL10), obinutuzumab + chlorambucil and rituximab + chlorambucil (CLL11), and ofatumumab + chlorambucil (COMPLEMENT-1). Median age across studies was 61-74 years, with older populations receiving ibrutinib, obinutuzumab + chlorambucil, or rituximab + chlorambucil. Median follow-up varied across studies/regimens (range 14.5-37.4 months). Among all patients, PFS appeared longer with ibrutinib relative to CIT and OS appeared comparable. Relative to CIT studies that similarly excluded patients with del(17p) (CLL10) or enrolled older/less-fit patients (CLL11), PFS appeared favorable for ibrutinib in high-risk subgroups, including advanced disease, bulky lymph nodes, unmutated IGHV status, and presence of del(11q). Grade ≥ 3 infections ranged from 9% (ofatumumab + chlorambucil) to 40% (fludarabine + cyclophosphamide + rituximab), and was 25% with ibrutinib. Grade ≥ 3 neutropenia was 12% for ibrutinib and 26%-84% for CIT. Although definitive conclusions cannot be made due to inherent limitations of cross-trial comparisons, this report suggests that ibrutinib has a favorable benefit/risk profile and may potentially eliminate the need for chemotherapy in some patients. Randomized, comparative studies are needed to support these findings., (© 2018 The Authors. American Journal of Hematology published by Wiley Periodicals, Inc.)

A retrospective cohort study was set up to analyse the prevalence and treatment of obstructive sleep apnoea (OSA) in relation to the severity of the deformity in patients with craniofacial microsomia (CFM). This study included a population of 755 patients with CFM from three craniofacial centres. Medical charts were reviewed for severity of the deformity, types of breathing difficulty, age at which breathing difficulty first presented, treatment for OSA, and treatment outcome. In total, 133 patients (17.6%) were diagnosed with OSA. Patients with Pruzansky IIB/III classification or bilateral craniofacial microsomia were significantly more often diagnosed with OSA than unilaterally affected patients of Pruzansky I/IIA classification. The initial treatment of OSA consisted of adenotonsillectomy, tracheotomy, or non-invasive positive pressure ventilation. Thirty-seven patients received more than one treatment (range 1-3). In this study, the prevalence of OSA in patients with CFM was higher than the prevalence in the healthy population described in the literature. Although several treatment modalities are available for the treatment of OSA in patients with CFM, treatment should be individualized and based on clinical symptoms, the severity of the deformity, and comorbidities., (Copyright © 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Participation in sport carries an increased risk of sustaining dental trauma which can be reduced by the use of a mouthguard. Mouthguards work by dissipating the force of impact, thus reducing the force which is transferred to the dentition. There are different types of mouthguard available which vary in design, costs and the level of protection provided. This article aims to review the use of mouthguards in sport, the common barriers to their use and also the different types of mouthguards and their characteristics.

Background: The optimal reduction of immunosuppressive therapy (IST) in renal transplant patients with post-transplant lymphoproliferative disorders (PTLDs) is uncertain. As chemotherapy is immunosuppressive, IST may be stopped during this time without compromising graft function. Subsequent long-term reduction of IST reduces relapse risk, but may increase risk of graft rejection., Methods: We performed a retrospective, matched cohort study of adult renal transplant patients in whom IST was ceased during chemotherapy and resumed at lower dose (calcineurin inhibitor at 50%, prednisolone ≤10 mg daily, no third agent) approximately 6 weeks after chemotherapy. Outcomes were compared with those of renal transplant patients without PTLD, matched for creatinine at equivalent time post-transplant that PTLD was diagnosed in cases, as well as for age, gender and year of transplant., Results: Twenty-four cases of PTLD occurring at a median of 9.2 years post-transplant were compared with 83 matched controls. PTLD cases were followed for a median of 11.9 years. Using competing risks analysis, time to 25% increase in serum creatinine was not significantly different between the two groups [adjusted hazard ratio (HR) 1.8, 95% confidence interval (CI) 0.89-3.6]. Similar results were obtained using multivariable Cox regression analysis (HR 1.19, 95% CI 0.44-3.23). Only one PTLD case experienced a ≥25% increase in creatinine <6 months after IST cessation in the setting of progressive PTLD and death. Three cases recommenced dialysis, compared with three controls (HR 2.5, 95% CI 0.47-13.00). Five-year patient survival rates for cases and controls were 70 and 94%, respectively (P = 0.01)., Conclusions: IST can be safely ceased during chemotherapy for PTLD in renal transplant patients. Furthermore, long-term reduction in IST is not associated with a significant difference in renal function deterioration. Prospective trials are needed to address the optimal reduction of IST in PTLDs., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Introduction: In this study, we compared the shear bond strengths of five different adhesive techniques for attaching metal orthodontic brackets onto acrylic pontics., Materials and Methods: Two hundred upper left lateral incisor acrylic teeth with bonded brackets were divided into five groups - composite alone (control), composite following sandblasting, composite held with a mechanical undercut, cyanoacrylate adhesive and Panavia(®). The initial bond strength was tested using the Instron Universal Testing Machine. The fatigue bond strength was tested by subjecting each bracket to 5000 repetitive low-load cycles at 50% of the mean shear bond strength using the Dartec machine at 2 Hz., Results: Cyanoacrylate adhesive statistically exhibited the highest mean bond strength (19·82 MPa). This was followed by the mechanical undercut group (17·69 MPa) and the sandblasted group (17·18 MPa). There was no statistically significant difference when considering the effect of fatiguing (p = 0·238) as well as the interaction between the adhesive technique and the effect of fatiguing on the bond strength (p = 0·440)., Conclusion: The initial and fatigue bond strengths of the cyanoacrylate adhesive, sandblasted and undercut groups were significantly higher than the control and Panavia(®) groups when tested under laboratory conditions.

Introduction: Research has shown that orthodontic patients are more likely to retain information presented in an audiovisual format. However, there has been little research on the effectiveness of audiovisual information provided through different routes such as the Internet. This parallel-group randomized controlled trial assessed whether provision of audiovisual information on the YouTube (Google, San Bruno, Calif) Web site to orthodontic patients undergoing fixed appliance treatment results in improved patient knowledge when compared with conventional methods of information provision. The effects of sex and ethnicity were also investigated., Methods: Participants were recruited from the Department of Orthodontics of the Eastman Dental Hospital, University College London Hospitals NHS Foundation Trust, United Kingdom. The patients were 13 years of age and over, with no history of orthodontic treatment, and patient and parental (where appropriate) consent were obtained. The participants were randomized into control (n = 34) and intervention (n = 33) groups using a random number table; there was stratification based on age group, with permuted blocks of 10 patients. Both groups were given routine verbal and written patient information related to fixed appliances, and the participants in the intervention group were sent 3 e-mails over 6 weeks requesting that they view a 6-minute YouTube video containing similar information but in audiovisual format. Patient knowledge was measured using identical questionnaires answered on the day of recruitment (baseline) and again 6 to 8 weeks later. The researchers were unaware of group allocations when enrolling patients and scoring questionnaires., Results: Sixty participants (89.55%) completed the study. Those who completed the trial in the intervention group (n = 30) demonstrated significantly greater improvements in knowledge than did those in the control group (n = 30), scoring, on average, almost 1 point more (95% CI for the difference, 0.305-1.602; P = 0.005) on the final questionnaire. Ethnicity had a statistically significant effect on improvement in knowledge, but sex did not. No harm to any patient was noted during the trial., Conclusions: Presenting audiovisual information through the YouTube Web site to orthodontic patients resulted in a significant improvement in patient knowledge. Supplementation of verbal and written patient information with audiovisual information via the Internet is therefore worthy of consideration., Registration: National Research and Ethics Service (REC number 12/LO/0863), United Kingdom., Protocol: The protocol was not published before trial commencement., Funding: No funding or conflict of interest to be declared., (Copyright © 2015 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Objective: To delineate the phenotype of early childhood epileptic encephalopathy due to de novo mutations of CHD2, which encodes the chromodomain helicase DNA binding protein 2., Methods: We analyzed the medical history, MRI, and video-EEG recordings of 9 individuals with de novo CHD2 mutations and one with a de novo 15q26 deletion encompassing CHD2., Results: Seizures began at a mean of 26 months (12-42) with myoclonic seizures in all 10 cases. Seven exhibited exquisite clinical photosensitivity; 6 self-induced with the television. Absence seizures occurred in 9 patients including typical (4), atypical (2), and absence seizures with eyelid myoclonias (4). Generalized tonic-clonic seizures occurred in 9 of 10 cases with a mean onset of 5.8 years. Convulsive and nonconvulsive status epilepticus were later features (6/10, mean onset 9 years). Tonic (40%) and atonic (30%) seizures also occurred. In 3 cases, an unusual seizure type, the atonic-myoclonic-absence was captured on video. A phenotypic spectrum was identified with 7 cases having moderate to severe intellectual disability and refractory seizures including tonic attacks. Their mean age at onset was 23 months. Three cases had a later age at onset (34 months) with relative preservation of intellect and an initial response to antiepileptic medication., Conclusion: The phenotypic spectrum of CHD2 encephalopathy has distinctive features of myoclonic epilepsy, marked clinical photosensitivity, atonic-myoclonic-absence, and intellectual disability ranging from mild to severe. Recognition of this genetic entity will permit earlier diagnosis and enable the development of targeted therapies., (© 2015 American Academy of Neurology.)

Hypodontia is a frequently encountered condition within general dental practice. Its successful management involves the interplay of a number of clinicians. The general dental practitioner plays a key role in the management of patients. The aim of this short article is to outline some of the principles of the multidisciplinary management of hypodontia with an emphasis on orthodontic treatment.

There has been a reported increase in the incidence of self-harm within the United Kingdom. This is of great concern, as a number of studies have shown self-harm to be a major risk factor to completed suicide. However, the identification of self-harm provides an opportunity for support and treatment. Mental health is an area that often receives little attention in the undergraduate dental curriculum. Yet dental practitioners, as healthcare professionals, need to be vigilant for any risk factors or signs of mental illness among their patients and make appropriate onward referrals. The purpose of this article is to examine the current evidence and aspects of self-harm, particularly in young adults and adolescents that are relevant within a dental settling.

Objective: To evaluate orthodontic practice websites for the reliability of information presented, accessibility, usability for patients and compliance to General Dental Council (GDC) regulations on ethical advertising., Setting: World Wide Web., Materials and Methods: The term 'orthodontic practice' was entered into three separate search engines. The 30 websites from the UK were selected and graded according to the LIDA tool (a validated method of evaluating healthcare websites) for accessibility, usability of the website and reliability of information on orthodontic treatment. The websites were then evaluated against the GDC's Principles for ethical advertising in nine different criteria., Results: On average, each website fulfilled six out of nine points of the GDC's criteria, with inclusion of a complaints policy being the most poorly fulfilled criteria. The mean LIDA score (a combination of usability, reliability and accessibility) was 102/144 (standard deviation 8.38). The websites scored most poorly on reliability (average 43% SD 11.7), with no single website reporting a clear, reliable method of content production. Average accessibility was 81% and usability 73%., Conclusions: In general, websites did not comply with GDC guidelines on ethical advertising. Furthermore, practitioners should consider reporting their method of information production, particularly when making claims about efficiency and speed of treatment in order to improve reliability.

Objective: The aims of this study were to (1) investigate if there is a difference in skeletal maturation between tooth agenesis and control patients and (2) whether skeletal maturation is affected by the severity of tooth agenesis. The cervical vertebral maturation (CVM) index can be used to assess skeletal maturation., Design: A retrospective cross-sectional study., Setting: Eastman Dental Hospital, London, UK., Methods and Materials: A total of 360 cephalograms of patients aged 9-17 years (164 males and 196 females) allocated to four subgroups (mild, moderate and severe tooth agenesis patients, and controls) were assessed retrospectively. There were 90 patients in each of the four subgroups. The skeletal maturation of each subject was assessed both quantitatively and qualitatively using the CVM index. All patients in the study were either currently receiving treatment or had been discharged from the hospital., Results: There was no statistically significant relationship between skeletal maturation and the presence of tooth agenesis. Furthermore, there was no statistically significant relationship between the skeletal maturity of patients and different severities of tooth agenesis., Conclusions: The data obtained from this group of patients and using this measurement tool alone does not supply sufficient reason to reject the null hypothesis. However, it suggests that it is possible that no difference exists between the groups.

Introduction: The aim of this study was to test the hypothesis that all blunt trauma patients, presenting with a Glasgow coma scale (GCS) score of 15, without intoxication or neurological deficit, and no pain or tenderness on log-roll can have any thoracolumbar fracture excluded without imaging., Materials and Methods: All patients diagnosed with a thoracolumbar fracture presenting to the emergency department of a major trauma centre and having an initial GCS score of 15 were included in the study. Variables collected included type of fracture, mechanism of injury, the presence of pain or tenderness on log-roll, ethanol levels and prehospital opioid analgesia., Results: There were 536 patients with thoracolumbar fractures, of which 508 (94.8%) patients had either pain, tenderness or had received prehospital opioid analgesia. A small subgroup of 28 (5.2%) patients who received no prehospital opioid analgesia, did not complain of pain and had no tenderness to the thoracolumbar spine elicited on log-roll. This subgroup was significantly older (p=0.033) and a high proportion of patients (64.3%) had a concurrent fracture of the cervical spine. Within this subgroup, a clinically significant unstable thoracic fracture was present in three patients, with all three patients exhibiting symptoms and signs of neurological injury or having a concurrent cervical vertebral fracture., Conclusions: In this population of blunt trauma patients with a GCS score of 15, not under the influence of alcohol or prehospital morphine administration, the absence of pain or tenderness on log-roll can exclude a clinically significant lumbar vertebral fracture, but does not exclude a thoracic fracture.

The immunoglobulin new antigen receptors (IgNARs) are a class of Ig-like molecules of the shark immune system that exist as heavy chain-only homodimers and bind antigens by their single domain variable regions (V-NARs). Following shark immunization and/or in vitro selection, V-NARs can be generated as soluble, stable, and specific high affinity monomeric binding proteins of ∼12 kDa. We have previously isolated a V-NAR from an immunized spiny dogfish shark, named E06, that binds specifically and with high affinity to human, mouse, and rat serum albumins. Humanization of E06 was carried out by converting over 60% of non-complementarity-determining region residues to those of a human germ line Vκ1 sequence, DPK9. The resulting huE06 molecules have largely retained the specificity and affinity of antigen binding of the parental V-NAR. Crystal structures of the shark E06 and its humanized variant (huE06 v1.1) in complex with human serum albumin (HSA) were determined at 3- and 2.3-Å resolution, respectively. The huE06 v1.1 molecule retained all but one amino acid residues involved in the binding site for HSA. Structural analysis of these V-NARs has revealed an unusual variable domain-antigen interaction. E06 interacts with HSA in an atypical mode that utilizes extensive framework contacts in addition to complementarity-determining regions that has not been seen previously in V-NARs. On the basis of the structure, the roles of various elements of the molecule are described with respect to antigen binding and V-NAR stability. This information broadens the general understanding of antigen recognition and provides a framework for further design and humanization of shark IgNARs.

Background: Multiple endocrine neoplasia, type 2B (MEN 2B), is an autosomal-dominant condition characterized by the development of multiple endocrine tumors. All affected people develop an aggressive form of medullary thyroid cancer (MTC). Without early prophylactic thyroidectomy, the prognosis for patients with MEN 2B is poor; the average age at death is 21 years., Case Description: The authors present a case of a 16-year-old girl who had a diagnosis of MEN 2B and was treated successfully for metastatic MTC., Clinical Implications: Given the striking orofacial manifestations of MEN 2B (marfanoid habitus; dolichocephaly; everted and thickened lips; mucosal neuromas on lips, tongue, buccal mucosa and eyelids), dental professionals are well positioned to recognize the disorder. Early identification of patients with the condition permits screening for preclinical thyroid disease, molecular genetic testing, counseling and lifesaving thyroid surgery.

Objective: To determine the influence of varying the width-to-height ratio of maxillary central incisors on perceived smile aesthetics., Design: Cross-sectional study., Setting: Postgraduate dental teaching hospital., Methods: A posed female smile was digitally modified using Adobe Photoshop(®). Three images were created; central incisors with normal form, tooth wear and delayed apical migration. For each image the length of the teeth was altered to create a set of nine images with normal form (66% to 96% width-to-height ratios), and sets of five images with tooth wear and with delayed apical migration (78% to 96% ratios). The images in each set were ranked in order of most to least attractive by 32 dentists, 32 technicians and 32 patients., Results: An 82% width-to-height ratio was perceived as the most attractive for normal central incisors although there is variability in the responses. There is a definite trend towards the extremes of very long or very short teeth being less attractive. The very long central incisors, and those with tooth wear were perceived as unattractive. The patients rated fewer images from the tooth wear and delayed apical migration sets as unattractive compared to the dentists and technicians., Conclusion: The width-to-height ratios perceived as most attractive correspond with the higher end of ideal ratios proposed in the dental literature (75-80% width-to-height ratio). Significant differences exist between the aesthetic perceptions of dentists, technicians and patients and there is lack of agreement within each group, in particular within the patient group. The individual variability in patient response should be taken into account during treatment planning.

The cartilaginous fish (chimeras, sharks, skates and rays) are the oldest group relative to mammals in which an adaptive immune system founded upon immunoglobulins has been found. In this manuscript we characterize the immunoglobulins of the spiny dogfish (Squalus acanthias) at both the molecular and expressed protein levels. Despite the presence of hundreds of IgM clusters in this species the serum levels of this isotype are comparatively low. However, analysis of cDNA sequences and serum protein suggests microheterogeneity in the IgM heavy chains and supports the proposal that different clusters are preferentially used in the two forms (monomer or pentamer) of this isotype. We also found that the IgNAR isotype in this species exists in a previously unknown multimeric format in serum. Finally, we identified a new form of the IgW isotype (the shark IgD orthologue), in which the leader is spliced directly to the first constant domain, resulting in a molecule lacking an antigen-binding domain., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Introduction: The aims of this study were to compare the radiographic development of permanent teeth in a group of children affected by dental agenesis with an unaffected control group and to determine the effects of confounding factors including the severity of the dental agenesis, age, sex, ethnicity, and the number of stages used to estimate dental age., Methods: A single-center retrospective cross-sectional study of dental panoramic tomographs was undertaken between July 2007 and April 2008 in a postgraduate teaching school. A total of 139 patients (aged 9-18 years) were recruited from the orthodontic clinic on the basis of predetermined inclusion and exclusion criteria to either a dental agenesis group or a control group. Dental panoramic tomograms were assessed, and the stages of development of the permanent teeth in the left maxillary and left mandibular regions were scored by using the 12 stages of Haavikko and the 8 stages of Demirjian and Goldstein. For each tooth scored, the mean dental age and standard error were determined by using the dental age assessment method, and an estimated dental age for each subject was derived by using the weighted average method., Results: A statistically significant delay in dental age was found in the patients with dental agenesis compared with the control group. The dental age assessment method of Haavikko showed a delay of 1.20 years (SD, 1.74), and the method of Demirjian and Goldstein showed a delay of 1.64 years (SD, 1.75). It was also observed that older patients with dental agenesis had greater delays in tooth formation (P <0.001). With the Haavikko method, for every year of chronologic age, the delay in dental age increased by 0.53 year; with the Demirjian and Goldstein method, the delay increased by 0.48 year. A significant association was seen between the severity of dental agenesis and the delay in dental age (P <0.01). With both methods, for each additional developmentally absent tooth, the dental age was delayed by 0.13 year (lower confidence interval, -0.22; upper confidence interval, 0.35). There was no evidence that sex or ethnicity has an effect on the delay in dental age in patients with dental agenesis., Conclusions: The development of permanent teeth in children with dental agenesis is delayed when compared with a matched control group. The severity of dental agenesis affected the magnitude of the delay (P <0.01). This delay has implications in orthodontic treatment planning and in the estimation of age for legal, immigration, archaeological, and forensic purposes., (Copyright © 2012 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.)

This report discusses the case of a 52 year old female with post-transplant lymphoproliferative disorder, confined to the central nervous system, which was managed with high dose methotrexate (HDMTX) in the context of end stage renal disease. The patient received two doses of HDMTX followed by extended hours high-flux hemodialysis, plasma methotrexate concentration monitoring and leucovorin rescue. The hemodialysis technique used was effective in clearing plasma methotrexate and allowed delivery of HDMTX to achieve complete remission with limited and reversible direct methotrexate-related toxicity. Dialysis-dependent renal failure does not preclude the use of HDMTX when required for curative therapy of malignancy.

Unlabelled: Compared to open surgery, laparoscopic treatment has been shown to have several advantages, including lower levels of postoperative pain, faster recovery, and better cosmetic results. Nevertheless, the advantages of laparoscopy are being debated as possibly not being merely related to biomedical factors., Material and Methods: The study consisted of two sub-studies. In the first study, 150 healthy, previously unoperated volunteers, not employed in the health services, were included. Healthy volunteers, from the latter study, were given questionnaires that presented different sizes of post-operative wounds and examined their perception of the severity of the illnesses that were treated by surgery leading to these wounds. In the second study, data was collected from 65 laparoscopic cholecystectomy patients and 35 patients treated by the open approach cholecystectomy. Patients from the second study were examined prior to operation and 1 month after surgery with a questionnaire evaluating their subjective perception of the disease., Results: Subjective perception of the severity of disease (SPSD) was similar between the laparoscopy and the open approach cholecystectomy patients before the operation (respectively, 6.25±1.7 and 6.06±2.2; ns). At the follow-up, a significant decrease of SPSD among laparoscopy patients was observed (post-op score = 3.28±0.8, p<0.05 in paired t-Student test), but not in the open approach patients (6.42±1.7, ns in paired t-Student test). The volunteers perceived that the disease of the laparoscopically treated patients was less serious than the disease of those treated with open surgery., Conclusions: The authors would like to emphasize that the study presents a new approach to the explanation of the so called "laparoscopy phenomenon", i.e. much faster and smoother recovery after relatively larger and more serious surgical procedures. We believe that the benefits observed among the videoscopy patients might be, apart from immunological and pain-related factors, attributed to the psychological influence of cognitive representations of the disease severity on pain, analgetics use, and recovery.

Objective: The aim of this study was to determine the influence of incisal edge embrasure space and interproximal contact area dimensions on perceived smile aesthetics., Design: Cross-sectional study., Setting: Postgraduate dental teaching hospital., Methods: A photograph of a smiling female, displaying only the lips and maxillary teeth was digitally altered. First, the proportions of the incisal edge embrasure spaces were modified to produce five different images. Secondly, the lengths of the interproximal contact areas were altered to produce five different images. The two sets of photographs were ranked from 'most attractive' to 'least attractive' by 35 dentists, 35 dental technicians and 35 patients., Results: An embrasure space arrangement where the size of the embrasures increases progressively distally from the midline was deemed most attractive; absence of embrasure spaces was deemed least attractive. In assessing the interproximal contact areas, all groups assessed an arrangement where the areas between the teeth were equal (and 50% the length of the central incisor) as most attractive, and where the contact areas increased in length progressively distally from the midline as least attractive. There were few statistically significant differences between the groups in these perceptions., Conclusion: Whilst there is broad agreement in what the participant groups deem to be aesthetic, our findings do not wholly correspond to the 'ideals' that have been previously suggested in the dental literature.

Aim: The aim of this study was to determine the possible effects of the 2006 National Health Service General Dental Services contract changes on the referral pattern to the orthodontic department at St George's Hospital, South West London., Method: This study was carried out on a retrospective basis. The notes of consecutive patients referred between 1st May and 30th September in 2005 and 2008 were assessed, and the patient's Index of Orthodontic Treatment Need (IOTN) and the source of referral noted., Results: The total numbers of referrals increased from 260 in 2005 to 405 in 2008. The number of referrals from general dental practitioners decreased slightly from 165 to 156, as did the numbers of referrals from other sources, such as tertiary referrals. The number of referrals made by specialist practitioners increased from 41 in 2005 to 207 in 2008, representing an increase from 16% to 51% of overall referrals. Overall, the number of patients being referred with an IOTN dental health component grade of 5 increased from 27% to 55%., Conclusion: The increase in referrals from specialist practitioners may be partly due to the changes brought to the commissioning of orthodontic services for specialist practitioners. Overall, the number of cases being referred with IOTN grades 4 and 5 remains high at St George's Hospital, indicating that appropriate referrals are being made.

Aim: To assess the quality of information included in referral letters sent to the orthodontic department at Kingston Hospital, Surrey, UK., Methods: Referral letters sent by both general dental practitioners (GDPs) and specialist orthodontists were analysed retrospectively in order to ascertain the percentage meeting the inclusion criteria as suggested by Mossey (2006) and the British Orthodontic Society (2008) for the quality of information included in an ideal orthodontic referral letter. Thirty-five consecutive letters sent between May and September 2005 and 206 letters sent in the same period in 2008 were collected by hand and analysed against the inclusion criteria. The numbers of referral letters received from GDPs, specialist orthodontists, and others sources were also determined., Results: Most of the referrals sent in 2005 and 2008 included 40-50% of the referral inclusion points. This was despite an almost twofold increase in the number of referral letters received from specialist orthodontic practitioners in 2008. The majority of the letters, from both GDPs and specialists, did not include details of the oral hygiene or caries status of the patient, or an indication of their motivation towards treatment. None of the referral letters included a plaque score., Conclusion: The main weaknesses in the quality of information provided in referral letters were that in more than 80% of the letters there was no mention of the patient's medical history and no comment on caries status, the standard of oral hygiene, patient motivation for treatment, or an Index of Orthodontic Treatment Need score. The quality of information included in referral letters sent to Kingston Hospital orthodontic department needs to be improved.

Careful management of the occlusion is necessary for successful prosthodontic treatment. A reorganized occlusal approach requires a more accurate registration of the desired jaw position, and where it is difficult to achieve this, an occlusal splint is indicated. This clinical report documents a 60-year-old man with a Prosthodontic Diagnostic Index Class IV dentition, who prior to a full-mouth reconstruction, underwent occlusal splint therapy with a Michigan-type splint that incorporated z-springs to allow concurrent orthodontic tooth movement of two anterior teeth to positions that would allow favorable restorations by correcting occlusal and esthetic form.

Angelman syndrome is often associated with an intractable seizure disorder. We describe 4 children who demonstrated an excellent response to corticosteroid therapy. The benefits included not only reduction in clinical seizures but also modification of the "typical'' Angelman electroencephalogram. In addition, there was improvement in the myoclonic jerks, sleep pattern, and developmental progress. Corticosteroids appeared to have a broad benefit on the epileptic encephalopathy. We believe that these cases pose a challenge to the conventional management of intractable epilepsy in Angelman syndrome.