Rare and Common Variants Conferring Risk of Tooth Agenesis.

We present association results from a large genome-wide association study of tooth agenesis (TA) as well as selective TA, including 1,944 subjects with congenitally missing teeth, excluding third molars, and 338,554 controls, all of European ancestry. We also tested the association of previously identified risk variants, for timing of tooth eruption and orofacial clefts, with TA. We report associations between TA and 9 novel risk variants. Five of these variants associate with selective TA, including a variant conferring risk of orofacial clefts. These results contribute to a deeper understanding of the genetic architecture of tooth development and disease. The few variants previously associated with TA were uncovered through candidate gene studies guided by mouse knockouts. Knowing the etiology and clinical features of TA is important for planning oral rehabilitation that often involves an interdisciplinary approach.

Oral health in young individuals with foreign and Swedish backgrounds--a ten-year perspective.

AIM: To investigate oral health status and coherent determinants in children with foreign backgrounds compared with children with a Swedish background, during a ten year period. DESIGN AND METHODS: In 1993 and 2003, cross-sectional studies with random samples of individuals in the age groups 3, 5, 10 and 15 years were performed in Jönköping, Sweden. All the individuals were personally invited to a clinical and radiographic examination of their oral health status. They were also asked about their attitudes to and knowledge of teeth and oral health care habits. The final study sample comprised 739 children and adolescents, 154 with a foreign background (F cohort) and 585 with a Swedish background (S cohort). RESULTS: In both 1993 and 2003, more 3- and 5 year olds in the S cohort were caries-free compared with the F cohort. In 1993, dfs was higher among 3- and 5 year olds in the F cohort (p<0.01) compared with the S cohort. In 2003, dfs/DFS was statistically significantly higher in all age groups among children and adolescents in the F cohort compared with the S cohort. When it came to proximal tooth surfaces, the percentages of individuals who were caries-free, with initial carious lesions, with manifest carious lesions and with restorations among 10-year-olds in the F cohort were 55%, 23%, 4% and 18% in 1993. The corresponding figures for the S cohort were 69%, 20%, 6% and 5% respectively. In 2003, the values for the F cohort were 54%, 29%, 4% and 13% compared with 82%, 12%, 1% and 5% in the S cohort. In 2003, the odds of being exposed to dental caries among 10- and 15-yearolds in the F cohort, adjusted for gender and age, were more than six times higher (OR=6.3, 95% CI:2.51-15.61; p<0.001) compared with the S cohort. CONCLUSIONS: There has been a decline in caries prevalence between 1993 and 2003 in all age groups apart from 3-year-olds. However, the improvement in dfs/DFS was greater in the S cohort compared with the F cohort in all age groups. The difference between the F and S cohorts in terms of dfs/ DFS was larger in 2003 compared with 10 years earlier. In 2003, the odds ratio for being exposed to dental caries was almost six times higher for 10- and 15-year-olds with two foreign-born parents compared with their Swedish counterparts.

Prevalence of symptoms and signs indicative of temporomandibular disorders in children and adolescents. A cross-sectional epidemiological investigation covering two decades.

AIMS: These were to 1) estimate the prevalence of subjective symptoms and clinical signs of temporomandibular disorders (TMD) in children and adolescents in the city of Jönköping, Sweden, 2) follow possible variations in TMD signs and symptoms over a 20-year period, and 3) study possible associations between TMD symptoms and signs and factors of interest. DESIGN: About 100 individuals in the age groups of 3, 5, 10 and 15 years participated in cross-sectional stratified epidemiological investigations in 1983, 1993 and 2003. METHODS: All participants were asked to fill in a questionnaire including questions on general and oral health, dental care habits and some socio-demographic issues. More specific questions recorded the presence or absence of subjective symptoms: tiredness in the jaws on awakening or during chewing; clicking sounds or crepitations from the temporomandibular joints (TMJs); locking/ catching of the mandible; luxation of the mandible; reduced jaw movement capacity; pain during jaw movements; other pain conditions in the jaws or in the TMJ regions. Subjects were examined clinically at each time period for; jaw mobility (maximum jaw opening including vertical overbite, maximum laterotrusion to the right and to the left, maximum protrusion); TMJ function (normal function, deflection on jaw opening of >2 mm, TMJ clicking or crepitations, TMJ locking, TMJ luxation); pain on jaw movement (no pain on movements, pain on one movement, pain on more than one movement); muscle pain (no muscle pain, pain on palpation in 1-3 sites, pain on palpation in >3 sites); TMJ pain (no joint pain, pain on lateral palpation of one or both joints, pain on posterior palpation of one or both joints). No functional examination of the masticatory system was performed in children aged 3 and 5 years. RESULTS: TMD-related symptoms were very rare in 3- and 5-year-olds. In the age groups of 10- and 15-year olds, 5-9% of the participants reported more severe symptoms, up to 50% showed one or more TMD signs, while it was estimated that 1-2% were in need of TMD treatment. Several symptoms and signs increased with age. No gender differences, with the exception of recurrent headache, were noted. Oral parafunctions were reported by 11-47%. Apart from a few variables, no statistically significant changes in the prevalence of TMD symptoms and signs were observed over the 20-year period. Clenching/grinding of teeth and general health factors were found to be associated with TMD symptoms and signs. CONCLUSIONS: The prevalence of more severe TMD symptoms and signs in children and adolescents was generally low in all three examinations and did not change significantly during the 20-year period. Increasing age, general health factors and oral parafunctions were associated with TMD symptoms and signs in 10- and 15-year-olds.

A 20-year follow-up study of endodontic variables and apical status in a Swedish population.

AIM: To re-examine a population after 20 years and evaluate changes in prevalence of endodontic treatment and apical periodontitis, as well as the technical quality of root fillings. METHODOLOGY: One hundred and fifteen out of an original 200 patients living in the northern part of Sweden were re-examined with a full mouth radiographic survey after 20 years. Frequencies of root canal treated teeth, apical periodontitis and quality parameters of root fillings were registered. RESULTS: The frequency of root canal treated teeth increased significantly (P < 0.05) from 13.9% at the first investigation to 17.7% after 20 years. There was also a statistically significant increase (P < 0.05) in teeth with apical periodontitis from 3.3% to 6.8%. Apical periodontitis both in connection with root canal treated teeth and teeth without endodontic treatment, had increased during the follow-up period. Even though the quality of the root fillings had improved, there was no corresponding improvement of the apical status in teeth with root fillings. CONCLUSIONS: There is still a great need for endodontic treatment in the Swedish population, and no improvement in apical health was found during this 20-year follow up.

Summary and conclusions from the SIWI seminar for young water professionals food and urban security--breaking the urban/rural division in water management.

At the Seminar for Young Water Professionals, a group of young people from different parts of the world met to discuss and debate: the interface between the urban and rural environment--how can water management see to the interest of both the farmer and the urban citizen; how the spatial boundaries within water resources management will develop in the future due to changing population patterns. Three key themes crystallized during the day: the challenges of the urban/rural interface, the need for new boundaries in water resources management and the importance of site-specific, appropriate solutions in relation to water re-use.

Prediction of demand for treatment of temporomandibular disorders based on a 20-year follow-up study.

The purpose was to test the hypothesis that signs and symptoms characteristic of temporomandibular disorders (TMD) at age 15 would predict demand for treatment during a 20-year follow-up period. Of originally 135 examined 15-year-old subjects, 103 completed a questionnaire and 84 were examined clinically at the 10-year follow-up (at age 25). After 20 years (at age 35), 114 completed a questionnaire and 100 were also examined clinically. During the 20-year follow-up period, 21 subjects received some kind of treatment of TMD. At baseline (age 15), the treated group reported tooth grinding at night more often than the non-treated group (P = 0.0042). At the 10-year follow-up (at age 25), the treated group reported more symptoms of TMD and oral parafunctions than the non-treated group. Among the clinical registrations, there was only one significant difference between the groups: anterior tooth wear was more extensive in the treated group. At the 20-year follow-up (at age 35), the treated group reported significantly more symptoms of TMD and oral parafunctions than the non-treated group. The clinical dysfunction index was also higher in the treated group. Logistic regression revealed tooth grinding at night as a significant predictor of received treatment of TMD. However, the positive predictive value was low whereas the negative predictive value was high (90%). The findings indicate that nocturnal tooth grinding is related to demand for treatment of TMD.

Restoring endodontically treated teeth: a survey of current opinions among board-certified prosthodontists and general dental practitioners in Sweden.

PURPOSE: The main aim was to investigate the current opinions among general dental practitioners and board-certified prosthodontists in Sweden on how to restore root-filled teeth. MATERIALS AND METHODS: A questionnaire containing 31 multiple-choice questions was mailed to 892 general practitioners and 150 board-certified prosthodontists in Sweden. The questions asked for information on when the clinicians used posts in endodontically treated teeth and what kind of clinical procedure they used. They were also asked if they believed that a post strengthened a root-filled tooth. RESULTS: Sixty percent of the general practitioners and 67% of the prosthodontists returned the questionnaire. Twenty-nine percent of the responding general practitioners and 17% of the prosthodontists were of the opinion that a post reinforces a root-filled tooth. Only a few clinicians used posts "always" or "most of the time" when restoring endodontically treated teeth with fillings, while the vast majority used posts when restoring such teeth with crowns or fixed partial dentures. In both groups of dentists, cast posts were most commonly used. Despite the present knowledge that parallel-sided posts have a significantly higher success rate than tapered cast posts, only a minority of Swedish dentists use parallel-sided posts. CONCLUSION: In contrast to the results of several current studies, a high proportion of both general practitioners and prosthodontists believe that a post reinforces an endodontically treated tooth. This is one probable explanation for the almost ubiquitous application of posts when teeth are restored with crowns or fixed partial dentures.

Individual prediction of treatment outcome in patients with temporomandibular disorders.

Out of 3159 patients referred to a specialist clinic of stomatognathic physiology, 1297 patients started treatment because of temporomandibular disorders. All those patients were divided into subgroups of patients with mainly muscular or TMJ symptoms, respectively. A prediction of the treatment outcome as good or dubious was also made. This prediction was based on the patient's history and the clinical findings. A total of 989 patients (76%) completed the treatment. They all graded the degree of improvement of their initial symptoms using a Numeric Rating Scale. An improvement of initial complaints of 50% or more was judged to be a relevant change. In 85% of the patients with mainly muscular symptoms, the treatment was predicted to have a good outcome. The corresponding figures for those patients with mainly TMJ symptoms were 93%. Not less than 88% of all the patients reported an improvement of 50% or more of their initial complaints. The possibility to predict the treatment outcome as good in patients with mainly muscular symptoms was very good: 90% fulfilled the criteria of a positive treatment result. For those with a dubious prognosis, 56% had a positive outcome of treatment. The possibility to predict treatment outcome as good in those with mainly TMJ symptoms was also very good: 94% responded positively on the treatment. Almost the same figure, 88%, of those with a poor prognosis had a positive treatment outcome.

A 20-year longitudinal study of subjective symptoms of temporomandibular disorders from childhood to adulthood.

The aims were to study the development over 20 years of reported temporomandibular disorders (TMD) symptoms in an epidemiologic sample and to analyze possible correlations between these symptoms and some other variables. Four hundred and two randomly selected 7-, 11- and 15-year-old subjects were originally examined by means of a questionnaire with regard to symptoms of TMD. The investigation was repeated after 4 5, 10, and 20 years, using the same method. After 20 years, when the original group had reached the age of 27 to 35 years, 378 individuals (94%) could be traced, and they were sent a questionnaire. Three hundred and twenty subjects (80% of the original sample, 85% of the traced subjects) completed and returned the questionnaire. There was a substantial fluctuation of reported symptoms over the 20-year period. Progression to severe pain and dysfunction of the masticatory system was rare. On the other hand, recovery from frequent symptoms to no symptoms was also rare. At the last examination 13% reported one or more frequent TMD symptom. The prevalence of bruxism increased with time, but other oral parafunctions decreased. Women reported TMD symptoms and headache more often than men. Correlations between the studied variables were mainly weak. The highest correlations found (rs = 0.4-0.5) were those between reported tooth clenching and tooth grinding and jaw fatigue. It can be concluded that in this epidemiologic sample, followed over 20 years from childhood to adulthood, a substantial fluctuation of TMD symptoms was found. Severe symptoms were rare, but 1 of 8 subjects reported frequent TMD symptoms at the last exam.

Changes in signs and symptoms of temporomandibular disorders following treatment with implant-supported fixed prostheses: a prospective 3-year follow up.

PURPOSE: The aim was to investigate whether the replacement of lost teeth with implant-supported fixed prostheses (IFP) had any influence upon the signs and symptoms of temporomandibular disorders (TMD). MATERIALS AND METHODS: The subjects comprised 78 consecutive patients referred to a specialist clinic for treatment with IFPs. All were examined with respect to the presence of signs and symptoms of TMD before the start of treatment and after 1 and 3 years. RESULTS: Before treatment began, 21% of the patients were found to have moderate (15%) or severe (5%) clinical signs of dysfunction according to the Helkimo index. These figures decreased numerically but not statistically significantly to 10% and 1%, respectively, at the 3-year follow up. Nearly half of the patients (45%) reported one or more subjective symptoms of TMD at the first examination. The anamnestic index used had decreased statistically significantly at the 3-year follow up, when the 5 variables composing the index had improved, but the improvement was statistically significant only for the variables joint sounds and pain when opening the mouth wide. All patients were satisfied with the treatment received. CONCLUSION: The results from the present investigation show that treatment with IFPs has a good and lasting effect on the functional status of the masticatory system as well as on subjective symptoms of TMD and chewing ability in the vast majority of patients treated.

A longitudinal epidemiologic study of signs and symptoms of temporomandibular disorders from 15 to 35 years of age.

AIMS: To study the development over 20 years of signs and symptoms of temporomandibular disorders (TMD) in an epidemiologic sample and to analyze possible correlations between these signs and symptoms and some other variables. METHODS: The original group comprised 135 randomly selected 15-year-old subjects who were examined clinically and by means of a questionnaire for signs and symptoms of TMD. The examination was repeated after 5, 10, and 20 years by the same methods. After 20 years, when the original group had reached the age of 35 years, 124 individuals (92%) could be traced, and they were sent a questionnaire and invited for a clinical examination. The response rate was high: 114 subjects (92%) completed and returned the questionnaire, and 100 subjects (81%) attended the clinical examination. RESULTS: There was a substantial fluctuation of both reported symptoms and clinically recorded signs over the 20-year period, but progression to severe pain and dysfunction of the masticatory system was rare. In both the 15-year-old and 35-year-old subjects, 13% reported 1 or more frequent TMD symptoms. At age 35, only 3 subjects (3%) were classified as having severe or moderate clinical signs of dysfunction according to the Helkimo Index, fewer than in previous investigations. Women reported TMD symptoms and headache and had muscle tenderness and joint sounds more often than men. Correlations between the studied variables were mainly weak. Among the highest correlations found (rs = 0.4) were those between reported clenching and bruxing habits and TMJ sounds and jaw fatigue. CONCLUSION: In this epidemiologic sample followed from age 15 to 35 years, a substantial fluctuation of TMD signs and symptoms was found over time. Progression to severe pain and dysfunction was extremely rare.

Craniofacial morphology in 6-year-old Icelandic children.

The purpose of the study was to describe the craniofacial characteristics of 6-year-old Icelandic children, make a normative standard for children with an Angle Class I molar relationship, and compare them to those with an Angle Class II molar relationship. The material consisted of the radiographs of 363 children, 184 (50.7 per cent) boys and 179 (49.3 per cent) girls with a mean age of 6 years 7 months (range: 5 years 7 months-7 years 8 months). Twenty-two reference points were digitized and processed by standard methods with the Dentofacial Planner computer software program. The 33 variables calculated included both angular and linear. Two sample t-tests were used to study the differences between different groups. Only minimal differences could be noted between sexes in sagittal and vertical angular measurements. Linear measurements, on the other hand, were usually larger for the boys. When compared with Norwegian material of the same age group, similar trends were observed between sexes in both studies, but the Icelandic children showed slightly more mandibular prognathism and a lower mandibular plane angle. When compared with children with an Angle Class I molar relationship, children with an Angle Class II molar relationship did not have a different maxillary prognathism nor a different mandibular length. Cranial base dimensions were all significantly greater and the cranial base flexure was also significantly more obtuse in the distal group.

Therapeutic jaw exercises and interocclusal appliance therapy. A comparison between two common treatments of temporomandibular disorders.

From a total of 1344 consecutive patients referred to a TMD clinic, twenty-six patients fulfilled the strict inclusion criterias of TMD of mainly muscular origin. Half of the patients were assigned to receive treatment with an interocclusal appliance, the treatment being performed by a dentist. The other half was instructed to perform individualized therapeutic jaw exercises, and this treatment was managed by a dental assistant. The treatment result was evaluated after six months. The two treatments had a positive and equal effect upon both signs and symptoms of TMD. A further follow-up by questionnaire one to four years after the final clinical examination showed a lasting treatment result in most patients. Many patients, however, continued to perform jaw exercises and/or to wear their appliances. This indicates that these two treatments are mostly symptomatic and not causal. The conclusion of the present investigation is that therapeutic jaw exercises, managed by a dentist or a dental assistant, is a cost effective treatment with a prognosis comparable to a treatment with an interocclusal appliance and can thus be recommended as the first therapy of choice in patients with TMD of mainly muscular origin.

Synergism between 5-HT1B/1D and 5-HT1A receptor antagonists on turnover and release of 5-HT in guinea-pig brain in vivo.

The effects on 5-HT turnover (5-HIAA/5-HT ratio) and extracellular 5-HT and 5-HIAA levels (in vivo microdialysis in freely moving animals) were analysed in guinea-pig brains following the 5-HT1B receptor antagonist, GR 127935 [N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl-4'-(5-methyl-1 ,2,4-oxadiazol-3-yl) [1,1-biphenyl]-4-carboxamide], or the 5-HT1A receptor antagonist, WAY-100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride), administered alone or in combination. GR 127935, injected alone, increased 5-HT turnover with maximal effects approximately 50% above the control levels in the four brain regions examined (hypothalamus, hippocampus, striatum and frontal cortex). GR 127935 significantly increased extracellular concentrations of 5-HT and 5-HIAA in frontal cortex (40%), whereas 5-HIAA, but not 5-HT, was elevated in striatum (20-30%). WAY-100635 did not significantly change 5-HT turnover but caused a small significant increase in the extracellular 5-HT and 5-HIAA concentrations in both striatum and frontal cortex. The combined treatment with GR 127935 and WAY-100635 resulted in an increased 5-HT turnover reaching maximal effects of 70-90% above the control values in all brain regions tested and produced a significant elevation of striatal and frontal cortex extracellular 5-HT (40% and 60%, respectively) and 5-HIAA (60% and 70%, respectively) concentrations. The synergistic effect of the two receptor antagonists on the 5-HT turnover and the terminal release of 5-HT indicate somatodendritic 5-HT release and stimulation of inhibitory 5-HT1A receptors at this level. Extracellular 5-HIAA seems to be a better marker than 5-HT itself for the evoked 5-HT release when the reuptake mechanism is intact.

Pure alexia and word-meaning deafness in a patient with multiple sclerosis.

OBJECTIVE: To describe pure alexia and auditory comprehension problems in a young woman with multiple sclerosis (MS). PATIENT: A 33-year-old woman with MS who complained of difficulties in reading and comprehending spoken language was referred for a neuropsychological examination. Reading difficulties were confirmed and most of the reading errors were additions, omissions, and substitutions of single letters. While the patient reported that the letters seemed to disappear before her eyes, no general problems with visual attention, visual discrimination, or scanning were detected. No difficulties with spelling were reported. The auditory comprehension deficit is interpreted as a form of a semantic access disorder and is not due to generalized slowing in information processing or conceptual disintegration. CONCLUSIONS: Pure alexia is unusual in MS and to our knowledge only 1 other case has been reported (in Japanese). Memory impairments and slowed information processing are probably the most frequent cognitive sequelae of the disease and, consequently, the literature is biased toward the study of those cognitive domains. However, given the wide distribution of sclerotic plaques in MS, it could be argued that we should expect some variability of cognitive changes in MS. Striking deficits as seen in this patient should make us more sensitive to this possibility.

Influence of 5-HT1B/1D receptors on dopamine release in the guinea pig nucleus accumbens: a microdialysis study.

To clarify whether serotonin (5-HT) 5-HT1B/1D receptors are involved in dopamine (DA) release, extracellular levels of DA were monitored by in vivo microdialysis during various conditions. 5-HT (10 microM) alone, and together with the 5-HT1B/1D receptor antagonist. GR127935 (10 microM), or the 5-HT1B/1D agonist, sumatriptan (1 microM), were perfused into the nucleus accumbens of freely moving guinea pigs. A 10-fold increase in the extracellular concentration of DA was obtained during administration of 5-HT alone. The 5-HT-induced DA elevation was not significantly affected by co-administration of sumatriptan (MANOVA; P > 0.05) but markedly attenuated by coperfusion of GR127935 (MANOVA; P = 0.02). Neither GR127935 nor sumatriptan, when administered alone, significantly affected extracellular DA levels. These results suggest that, in the DA-rich nucleus accumbens, 5-HT1B/1D receptors are not involved in the modulation of DA release during normal tonic or basal conditions but may take part in the regulation of DA release when synaptic 5-HT levels are very high.

Prevalence of malocclusion in 6-year-old Icelandic children.

The prevalence of different malocclusion features was investigated in 396 6-year-old Icelandic children, using the epidemiologic registration method described by Björk et al. in 1964. Girls were ahead of boys with regard to dental stage (P < 0.01). One or more permanent teeth were congenitally missing in 5% of the children. Postnormal occlusion was found in 27% of the boys and in 31% of the girls, and prenormal occlusion was found in 6% and 5%, respectively. Straight terminal plane at the second deciduous molars was found in individuals with either normal or postnormal occlusion. Thus, it can be misleading to use the relation of the terminal planes as a measurement of the sagittal relation between the jaws. The prevalence of hypodontia was much lower than has been reported previously for Icelandic children.

[Non-convulsive status epilepticus. A rare but important reason for prolonged loss of conciousness.].

Non-convulsive status epilepticus is a rare form of epilepsy. The predominant clinical feature is prolonged loss of consciousness without prominent motor features. The diagnosis is often difficult because of the non-specific nature of the symptoms and this diagnostic possibility has to be born in mind when patients present with unexplained alteration in the level of consciousness, especially if there is a prior history of epilepsy. The electroencephalogram plays a key role in the diagnosis and intravenous administration of diazepam is a useful diagnostic test, especially in conjunction with EEG. We present three patients recently diagnosed in Iceland.

Evaluation of technical quality of endodontic treatment--reliability of intraoral radiographs.

The purpose of this study was to evaluate: 1) the use of the conventional buccolingual radiographic projection for estimating the technical quality of endodontic treatment and 2) the effect of the surrounding tissues on these evaluations. The material consisted of three radiographs of each of 108 extracted roots: a clinical radiograph, an in vitro radiograph taken in the buccolingual projection, and an in vitro radiograph taken in the mesiodistal projection. The radiographs were analysed by two observers and consensus was reached and used in the analyses. The agreement between the two observers was good, but statistically significant differences were found between recordings of the seal in the clinical radiographs and the in vitro radiographs taken in the buccolingual projection. The length of the root filling in each of the three projections was interpreted to be the same, while both inadequate seal and visible lumen apical to the root filling were recorded less frequently in the clinical radiographs than in either of the two in vitro projections. This difference was most pronounced in molar teeth. It was concluded that the lengths of root fillings could be measured correctly in clinical radiographs. Due to the anatomy of root canals in incisors and canines, there was a risk of misinterpreting an inadequate seal as adequate in these teeth. The large amount of tissue surrounding molar teeth tended to cause an underregistration of both inadequate seal and lumen apical to the root fillings in these regions.

Prevalence of gingivitis in 6-year-olds in Reykjavik, Iceland.

As part of a wider investigation of malocclusion, the aim of this study was to determine the prevalence of gingivitis in 6-year-olds in Reykjavik. Parents and guardians of the 401 children in 8 schools were invited by letter to have their children take part. There were 230 positive replies (57%). The Gingival Bleeding Index was used to determine the condition of the gingiva on mesiobuccal and buccal surfaces of 6 selected teeth (totaling 12 surfaces). The results showed that 26% had healthy gingivae, 23% showed bleeding from one surface, 20% from two, 17% from three, and 15% from four to eight surfaces. There were no statistically significant differences in the number of bleeding surfaces between boys and girls. The mean GBI for the whole group was 16%. Gingivitis in this group was therefore prevalent but usually slight.