[Whether or not to remove root remnants in frail older adults?] / Wel of niet wortelresten verwijderen bij kwetsbare ouderen?

Many frail older adults have a poor oral health: unrestorable broken teeth and root remnants with open root canals, commonly associated with periapical and periodontal inflammation, are often seen. Improving oral health in this growing group of frail older adults is a considerable challenge for dental care professionals. Dentists are often uncertain how to deal with root remnants and unrestorable broken teeth in psychogeriatric and/or medically compromised frail older adults. Decisions about the extraction or retention of root remnants should not only be made on the basis of preventing pain and inflammation, but also on the course of disease, life expectancy, cooperation, laws and regulations and other factors that are an issue in geriatric patients but not in regular (healthy) patients. To help oral health care professionals in their treatment choice for this complex patient group, a decision tree was developed in which both root and patient-related factors were included.

[Education and the dentist in 2025. An inventory of the gerodontology-programme for 5 Dutch and Flemish dental schools]. / Serie: Tandheelkundig onderwijs anno 2025. Een inventarisatie van het gerodontologie-onderwijs bij 5 Nederlandse en Vlaamse opleidingen tandheelkunde.

In a consensus meeting (September 2019) of the three Dutch and the two Flemish dental schools their current education programmes on gerodontology were presented and discussed. The aim was to examine if these programmes were in line with the most recent (inter)national guidelines, such as those of the European College of Gerodontology and the recently introduced Dutch framework Oral Health Care (2020). Therefore, the competences regarding the domain of gerodontology were analysed to assess if students were prepared adequately to meet the oral health care needs of the ageing population. In the consensus meeting a new set of competences was formulated together with a new outline for the gerodontology-programme applicable for the Dutch and Flemish dental schools.

[Can dental students and dental care providers in the Netherlands effectively and safely prescribe drugs?] / Serie: Onderwijs en de tandarts anno 2025. Kunnen tandheelkunde­studenten en mondzorgverleners in Nederland effectief en veilig geneesmiddelen voorschrijven?

Dentists and dental specialists are qualified to prescribe drugs. In this study, we assessed and compared the pharmacotherapeutic knowledge and skills of final year dental students, dentists and dental specialists in the Netherlands. In 2017, a random sample of these three groups was invited to complete an assessment. The knowledge assessment comprised 40 multiple choice questions covering often prescribed drugs. The skills assessment comprised three patient cases for which participants had to write a treatment plan. For the knowledge assessment, the response rates were 26 (20%) dental students, 28 (8%) dentists and 19 (19%) dental specialists, and for the skills assessment the response rates were 14 (11%) dental students, eight (2%) dentists, and eight (8%) dental specialists. On average, all three groups had inadequate knowledge scores (smaller 80%) and only a small proportion (smaller 30%) of their treatment plans was assessed as correct. These results suggest that dental students, dentists and dental specialists lack prescribing competence, which could be caused by poor pharmacotherapy education during under- and postgraduate dental training.

[Series: Education and the dentist in 2025. Evidence-based clinical practice guidelines for an academic learning line 'quality and safety in oral care']. / Serie: Onderwijs en de tandarts anno 2025. Op bewijs gebaseerde praktijkrichtlijnen in de opleiding; voorstel tot een academische leerlijn 'kwaliteit en veiligheid van mondzorg'.

Education in the field of quality and safety in oral care still needs further development, both for students and teachers. Based on the current development of clinical practice guidelines in the field of oral care in the Netherlands, this article describes a proposal for implementing this as a 'quality of oral care' learning line in the dental school curricula. Within clinical educational practice and scientific training, students should become familiar with the development, assessment and application of clinical practice guidelines. Some proposals for embedding this new learning line in the curriculum are given. In order to further shape the learning line, close cooperation between the three dental schools and the Kennisinstituut Mondzorg (Institute for Knowledge Translation in Oral Care) in the Netherlands is recommended.

[Effectivity and durability of telescopic dentures on abutment teeth]. / Doelmatigheid en duurzaamheid van telescoopprothesen op pijlerelementen.

In a study, the effectivity and durability of telescopic dentures on abutment teeth provided with telescope crowns were investigated. The prognosis for the prosthetic structure and for the abutment teeth were both investigated. The survival rate of 234 telescopic dentures (886 abutment teeth) in 147 patients in a general dental practice were retrospectively evaluated on the basis of a status study. The mean survival rate was calculated. This is the moment when 50% of the telescopic dentures had failed. For telescopic dentures in the maxilla, this was 22.3±2.8 years, which did not represent a statistically significant difference from the mandible (20.9±1.9 years). Of the 886 abutment teeth that were used, 127 (14.3%) were extracted after an average period of 11.7 years. Periodontal complications were the primary reason for extraction. Based on this investigation, one could conclude that telescopic dentures are also a durable and sustainable solution in the long term. Loss of abutment teeth is relatively rare and has limited influence on the survival of the prosthetic structure.

[Evidence-based clinical guidelines in dental practice 6. Guidelines for clinical practice in dental education]. / Evidencebased klinische praktijkrichtlijnen in de mondzorg 6. Praktijkrichtlijnen in de opleiding tot tandarts.

In response to the initiatives of the Kennisinstituut Mondzorg (Institute for Knowledge Translation in Oral Care), the importance of effective education in the area of guidelines is increasing. Future dentists will, after all, be confronted with new guidelines and need to be able to integrate them in their daily practice. Various guidelines and protocols have been established within the 3 dental schools. For students and instructors, however, the motivation for these guidelines and protocols is not always sufficiently clear. In addition, the terms guideline, clinical practice guideline and protocol are used interchangeably, resulting in terminological confusion. Embedding within and coordination with theoretical education is also still limited in all programmes and it is proposed that the 3 dental schools collaborate on this issue. Finally, it is advised to replace the term 'evidence-based' with 'evidence-informed' because this indicates more clearly that other factors (patients opinion, available financial means, etc.) play a role in the final choice of treatment in a specific situation.

Correlation of treatment-emergent adverse events and clinical response to endocrine therapy in early breast cancer: a retrospective analysis of the German cohort of TEAM.

BACKGROUND: Previous studies have suggested a correlation between the occurrence of vasomotor or joint symptoms during tamoxifen or aromatase inhibitor treatment and improved clinical response. PATIENTS AND METHODS: A retrospective analysis of the German cohort of the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial was carried out to assess disease-free survival (DFS) and overall survival (OS) in patients with and without arthralgia/myalgia and/or menopausal symptoms during adjuvant endocrine treatment. RESULTS: A total of 1502 patients were included; 739 patients received tamoxifen followed by exemestane and 763 received exemestane. Patients reporting arthralgia/myalgia and patients reporting menopausal symptoms during endocrine treatment had significantly longer OS and DFS than those not reporting these events. The effect on OS was irrespective of treatment. DFS was significantly improved in exemestane-treated patients reporting arthralgia/myalgia or those reporting menopausal symptoms versus those not reporting these events. This effect on DFS was not observed in patients receiving sequential treatment. A combined analysis of patients reporting either menopausal symptoms or arthralgia/myalgia showed that OS and DFS were significantly improved in patients reporting one of these symptoms versus those not reporting either symptom. CONCLUSION: The occurrence of arthralgia/myalgia or menopausal symptoms during endocrine treatment is associated with significantly improved OS.

Effects of exemestane and tamoxifen on hormone levels within the Tamoxifen Exemestane Adjuvant Multicentre (TEAM) trial: results of a German substudy.

AIM: The aim of this study was to compare the effects of exemestane and tamoxifen on hormone levels in postmenopausal patients with hormone receptor-positive breast cancer within a Germany substudy of the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial. METHODS: Within the TEAM trial, patients were randomized to receive adjuvant treatment with exemestane for 5 years or tamoxifen for 2.5-3 years followed by exemestane for 2-2.5 years. Serum levels of testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone binding globulin (SHBG), follicle stimulating hormone (FSH) and parathyroid hormone (PTH)-intact were measured at screening and after 3, 6 and 12 months of treatment. RESULTS: Data on hormone levels were available from 63 patients in the tamoxifen arm and 68 patients in the exemestane arm. Treatment with exemestane resulted in decreases from baseline in SHBG and PTH-intact levels, and increases from baseline in testosterone, DHEAS and FSH levels. Tamoxifen treatment resulted in increases from baseline in SHBG and PTH-intact, whereas levels of testosterone and FSH decreased and DHEAS levels did not change. At all time points assessed, the absolute change from baseline was significantly different between tamoxifen and exemestane for testosterone, SHBG, FSH and PTH-intact (all p < 0.0001). CONCLUSIONS: Exemestane and tamoxifen had statistically significantly different effects on hormone levels, including testosterone, SHBG, FSH and PTH-intact.

[Electives at the dental school in Groningen]. / Keuzeonderwijs binnen de opleiding Tandheelkunde Groningen.

To offer a more comprehensive curriculum in various dental topics, the dental school of the University of Groningen developed electives. This article gives an overview of the learning objectives of the different electives, the program and the way in which students are examined. Attention is also paid to some experiences of students and teachers with this kind of education. The electives seem to effectively prepare students for specific parts of dentistry, and they give an orientation on the scientific aspects of dentistry. Students and teachers are positive about the electives. The electives give good opportunities to the assessment of professional behavior.

Assessment of professional behaviour--a comparison of self-assessment by first year dental students and assessment by staff.

OBJECTIVE: A study was set up to assess usefulness and acceptability of a method of assessing professional behaviour of undergraduate dental students. SETTING: The first year preclinical course at the Department of Dentistry and Oral Hygiene, University of Groningen, the Netherlands. MATERIALS AND METHOD: A form was developed with an ordinal scale to assess undergraduate professional behaviour. A standard means of carrying out assessment was then undertaken and subsequently used to give feedback to the students at the end of each of three terms. The students' self-assessment was then compared to that of the staff. RESULTS: Descriptive analysis of the results was carried out per term. The response rate was 80-85%. The significant difference which existed between the scores of students and staff at the start of the study was reduced to reasonable agreement over two of the three criteria. CONCLUSIONS: The study indicated that the initial difference in assessment of their professional behaviour by first year dental students and by staff, was reduced by the forms and procedure used. This indicates the usefulness of the procedure as a teaching aid. The high participation rate confirms this to be an acceptable means of assessment of dental students' professional behaviour.

Functional roles of conserved transmembrane prolines in the human VPAC(1) receptor.

The importance of three conserved transmembrane prolines of the human vasoactive intestinal polypeptide (VPAC)(1) receptor was examined by single alanine substitution. P266A, P300A and P348A reduced the expression level, but maintained the binding to VIP. P266A showed decreased ability to stimulate cAMP, while P300A and P348A displayed an increased potency in cAMP production combined with a high sensitivity towards GTP compared to the wild type receptor. In addition, substitutions of two conserved leucines located in position -2 and +1 from P348 were investigated. L346A and L349A reduced the receptor expression, influenced the G protein coupling and decreased the receptor activity. These observations, which are the first on conserved transmembrane prolines within this family of receptors, indicate that these residues are important for receptor expression, G protein coupling and receptor activity.

Kinetic stability of designed glycosylation mutants of Coprinus cinereus peroxidase.

The effect of glycans and surface mutations on protein unfolding induced by heat or urea has been studied. Removal of the only native high mannose type glycan in the N142P, N142T, and N142D CIP mutants reduced the lifetime to half of that of wtCIP at irreversible conditions of unfolding. The effect was moderate at reversible conditions. Five glycomutants designed to have 0, 1, 2, 4 and 6N glycans showed a correlation between increased carbohydrate mass and increased stability toward irreversible unfolding. The results are in agreement with a dampening effect of glycans on backbone fluctuation in both the native and the unfolded states. However, experiments in reversible conditions were less clear because of additional effects of an increasing number of amino acid substitutions and aggregation. Examples of strong effects from minor surface changes were also observed.

A computer study of biodegradable plates for internal fixation of mandibular angle fractures.

PURPOSE: This computer-based study was performed to determine the suitability of small biodegradable plate systems for mandibular angle fractures. MATERIALS AND METHODS: In a 3-dimensional computer model of the mandible, fracture mobility and plate strain were calculated for bite forces applied on 13 bite points on the dental arch. The angle fracture was fixed with 2 polylactide (PLA) midiplates or with 2 PLA maxiplates. The first plate was positioned buccally on the external oblique ridge. Two positions of the second plate were studied: halfway up the height of the mandible or on the lower border. Maximum fracture mobility was set at a limit of 150 microm to enable undisturbed fracture healing. Maximum plate strain was set at the yield strain of PLA. RESULTS: Fixation with the PLA maxiplates, with the second plate positioned halfway up the height of the mandible, resulted in fracture mobility below the set limit for all bite points. For the other PLA fixation strategies, fracture mobility exceeded the set limit. Fixation with the second plate positioned halfway up the height of the mandible generally resulted in less fracture mobility than with the plate positioned on the lower border. The yield strain of PLA was not exceeded in any of the fixation strategies. CONCLUSIONS: Based on the computer model, 2 PLA maxiplates are suitable for fixation of mandibular angle fractures. One plate should be positioned buccally on the external oblique ridge, and the other should be positioned halfway up the height of the mandible.

Characterization of a G protein coupling "YL" motif of the human VPAC1 receptor, equivalent to the first two amino acids in the "DRY" motif of the rhodopsin family.

The conserved residues Y239 and L240 of human VPAC1 receptor are predicted to be at the same location as the asparagine and arginine in the "DRY" motif in the Rhodopsin family of G protein-coupled receptors. By comparing vasoactive intestinal peptide (VIP) binding with or without the presence of GTP-gamma-S, it was found that the deltadelta G(o) for the endogenous G-protein coupling was 1.5 kJ/mol, 0.95 kJ/mol, and 3.4 kJ/mol for theY239A, L240A, and wild-type receptor, respectively. VIP-induced cAMP production in whole cells support the results of the binding studies, as Y239A had a moderate and L240A a pronounced impaired ability to produce cAMP. The mutants had a minor influence on the intrinsic "low affinity to high affinity equilibrium," suggesting that the dominating effect of these mutants is a perturbation of the G protein-binding site. Thus, the highly diverged chemical properties of the hydrophobic "YL" motif and charged "DR(Y)" motif could be a crucial difference between the Secretin Receptor Family and the Rhodopsin Family with respect to receptor activation and G-protein coupling.

Creation of a selective antagonist and agonist of the rat VPAC(1) receptor using a combinatorial approach with vasoactive intestinal peptide 6-23 as template.

We have used combinatorial chemistry with amino acid mixtures (X) at positions 6 to 23 in vasoactive intestinal peptide (VIP) to optimize binding affinity and selectivity to the rat VPAC(1) receptor. The most efficient amino acid replacement was a substitution of alanine at position 18 to diphenylalanine (Dip), increasing the displacement efficiency of (125)I-VIP by 370-fold. The [Dip(18)]VIP(6-23) was subsequently used to find a second replacement, employing the same approach. Tyrosine at position 9 was selected and the resulting [Tyr(9),Dip(18)]VIP(6-23) analog has a K(i) value of 90 nM. This analog was unable to stimulate cAMP production at 10(-6) M but was able to inhibit VIP-induced cAMP stimulation (K(b) = 79 nM). The K(i) values of [Tyr(9),Dip(18)]VIP(6-23) using the rat VPAC(2) and PAC(1) receptors were 3,000 nM and >10,000 nM, respectively. Thus, [Tyr(9),Dip(18)]VIP(6-23) is a selective VPAC(1) receptor antagonist. The C-terminally extended form, [Tyr(9),Dip(18)]VIP(6-28), displays improved antagonistic properties having a K(i) and K(b) values of 18 nM and 16 nM, respectively. On the contrary, the fully extended form, [Tyr(9),Dip(18)]VIP(1-28), was a potent agonist with improved binding affinity (K(i) = 0.11 nM) and ability to stimulate cAMP (EC(50) = 0.23 nM) compared with VIP (K(i) = 1.7 nM, EC(50) = 1.12 nM). Furthermore, the specificity of this agonist to the VPAC(1) receptor was high, the K(i) values for the VPAC(2) and PAC(1) receptors were 53 nM and 3,100 nM, respectively. Seven other analogs with the [Tyr(9),Dip(18)] replacement combined with previously published VIP modifications have been synthesized and described in this work.

Role of second extracellular loop in the function of human vasoactive intestinal polypeptide/pituitary adenylate cyclase activating polypeptide receptor 1 (hVPAC1R).

To elucidate the functional role of the second extracellular loop of human vasoactive intestinal polypeptide/pituitary adenylate cyclase-activating polypeptide (VIP/PACAP) receptor (hVPAC1R), surface expression, ligand binding, and receptor activation were analyzed. Amino acids in the entire second extracellular loop were individually substituted by alanine by site-directed mutagenesis. The mutant and wild-type receptors were transiently expressed in HEK293 cells and purified cell membranes were tested for the ability to bind VIP, while the receptor activity was measured as potency of cAMP production analysed on intact cells. Surface expression of the substituted conserved residues, W286A, I289A, W294A, and W295A, was evidently decreased to 20-30% compared to the wild-type expression. W286A also showed an significantly reduced potency of cAMP production. Substituted residues as F280A, E281A, and G284A showed a significant reduction in the potency of stimulated cAMP production amounting to 8-46-fold, compared to the wild-type with unaffected surface expression and VIP binding. These results indicate that some residues in the second extracellular loop of the human VPAC1R participate in the active mechanism of a ligand-mediated response without being directly involved in the binding of VIP.

Immunohistochemical localization of the VIP1 receptor (VPAC1R) in rat cerebral blood vessels: relation to PACAP and VIP containing nerves.

The two structurally related peptides, vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP), are present in cerebral vascular nerve fibers. Biologic actions of VIP are exerted through two receptors, VPAC1 and VPAC2, having similar binding affinity for both VIP and PACAP. In the current study, the authors have developed a specific antibody against the rVPAC1 receptor to examine the localization of rVPAC1 immunoreactivity in cerebral arteries and arterioles of the rat by immunohistochemistry using fluorescence confocal microscopy. Specificity of the antiserum was ensured by immunoblotting and immunocytochemistry of cells transfected with cDNA encoding the different PACAP-VIP receptor subtypes. The rVPAC1 receptor immunoreactivity was localized to the plasmalemma of circularly orientated smooth muscle cells on superficial cerebral arteries and arterioles taken from the basal surface of the brain. By double immunostaining VIP immunoreactive nerve fibers and, to a lesser extent, those containing PACAP were shown to have intimate contact with the receptor protein. Vasoactive intestinal polypeptide and PACAP containing cerebrovascular nerve fibers were found in separate nerve populations with different distribution pattern and density. In brain sections processes of cortical VIP-, but not PACAP-, containing neurons seemed to innervate the rVPAC1 receptor of pial arterioles on the brain surface. The current findings provide the neuroanatomical substrate for a role of VIP and maybe PACAP in the regulation of cerebral blood flow.

A computer study of fracture mobility and strain on biodegradable plates used for fixation of mandibular fractures.

PURPOSE: This computer-based study was done to determine whether a small biodegradable plate system was suitable for internal fixation of mandibular fractures. MATERIALS AND METHODS: In a three-dimensional computer model of the mandible, fracture mobility and plate strain were calculated for bite forces applied on 13 bite points on the dental arch. Simulated solitary angle, body, and symphysis fractures were fixed with one titanium miniplate, one polylactide (PLA) midiplate, one PLA maxiplate, or two PLA midiplates. Fractures with and without interfragmentary bone contact were studied. In the case of fractures with bone contact, the loads were transmitted through the fracture surfaces and the plate; when there was no contact, the loads were transmitted only through the plate. Maximum fracture mobility was set at 150 microm. Maximum plate strain was set at the yield strain of PLA and titanium. RESULTS: For fractures without interfragmentary bone contact, all plate fixations resulted in a fracture mobility and plate strain higher than the limits set, except for the symphysis fracture fixed with two PLA midiplates. Interfragmentary bone contact significantly reduced fracture mobility and plate strain. For the angle fracture with bone contact, all PLA plate fixations resulted in a fracture mobility above the limit, whereas the titanium miniplate fixation had a fracture mobility below the limit. For the body and symphysis fracture with bone contact, only double PLA midiplate fixation resulted in a fracture mobility below the limit. CONCLUSIONS: From a mechanical point of view, based on the computer model, small PLA plates are only suitable for symphysis fractures with and without interfragmentary bone contact and for body fractures with interfragmentary contact. However, fixation with two PLA plates is always necessary to provide sufficient reduction of fracture mobility and plate strain.

Functional expression of rat VPAC1 receptor in Saccharomyces cerevisiae.

The yeast Saccharomyces cerevisiae was examined as host for heterologous expression of the G protein-coupled VPAC1 receptor. Rat VPAC1 receptor cDNA and two chimeric constructs encoding the yeast mating factor pre-pro alpha-leader peptide fused in-frame to rat VPAC1 receptor were expressed in yeast cells under control of a galactose inducible promoter. The rat VPAC1 receptor was fused to the HSV tag epitope to ensure proper immunological detection of the receptor. Crucial conditions for high-level expression of active rat VPAC1 receptor included growth in amino acid supplemented minimal medium, fusion to the yeast alpha-leader peptide and a temperature shift from 30 degrees C to 15 degrees C before promoter induction. Western blotting showed that the expressed receptor was highly glycosylated and a band of 47 kDa was obtained upon endoglycosidase H treatment. Binding with radioiodinated vasoactive intestinal polypeptide revealed a KD of 2.5 nM and an IC50 of 15 nM when displacing with unlabeled vasoactive intestinal polypeptide. VPAC1 receptor density quantified by Western blotting was 510 pmol/mg membrane protein of which only 66 pmol/mg were able to bind vasoactive intestinal polypeptide.

Adapting protein solubility by glycosylation. N-glycosylation mutants of Coprinus cinereus peroxidase in salt and organic solutions.

Protein solubility is a fundamental parameter in biology and biotechnology. In the present study we have constructed and analyzed five mutants of Coprinus cinereus peroxidase (CIP) with 0, 1, 2, 4 and 6 N-glycosylation sites. All mutants contain Man(x)(GlcNAc)(2) glycans. The peroxidase activity was the same for wild-type CIP and all the glycosylation mutants when measured with the large substrate 2,2'-azino-bis(-3-ethylbenzthiazoline-6-sulfonic acid). The solubility of the five CIP mutants showed a linear dependence on the number of carbohydrate residues attached to the protein in buffered solution of both ammonium sulfate (AMS) and acetone, increasing in AMS and decreasing in acetone. Moreover, the change in free energy of solvation appears to be a constant, though with opposite signs in these solvents, giving DeltaDeltaG degrees (sol)=-0.32+/-0.05 kJ/mol per carbohydrate residue in 2.0 M AMS, a value previously obtained comparing ordinary and deglycosylated horseradish peroxidase, and 0. 37+/-0.10 kJ/mol in 60 v/v% acetone.