[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.

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.

Crystallization and X-ray diffraction analysis of recombinant Coprinus cinereus peroxidase.

Crystals suitable for an X-ray diffraction investigation have been obtained of recombinant Coprinus cinereus peroxidase expressed in Aspergillus oryzae. The crystals were grown by the hanging drop method with polyethylene glycol 6000 as the precipitant. A pH range from 6.2 to 8.0 and CaCl2 or MgCl2 present at a concentration of 0.35 M were essential for the crystal growth. A metastable monoclinic modification can be obtained under certain conditions, and with variations in temperature they are transformed into a stable orthorhombic modification. With CaCl2 as the additive, the unit cell dimensions were a = 74.9 A, b = 76.8 A and c = 128.2 A. With two peroxidase molecules per asymmetric unit, the solvent content is 49% (v/v). In the diffraction pattern, the reflections Okl are systematically very weak for k = 2n + 1. Combined with an analysis of the Patterson function, this showed that the two independent molecules are related by the pseudotranslational symmetry 0.29a + 0.5b. The possible space groups are P2(1)2(1)2(1) or P2(1)22(1) because of this pseudosymmetry. The crystals diffract to a resolution of 2.9 A.

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.

[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.

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.

Glycosylation and thermodynamic versus kinetic stability of horseradish peroxidase.

The influence of N-linked glycans on the stability of glycoproteins has been studied using horseradish peroxidase isoenzyme C (HRP), which contains eight asparagine-linked glycans. HRP was deglycosylated (d-HRP) with trifluoromethanesulfonic acid and purified to an enzymatically active homogeneous protein containing (GlcNAc)2 glycans. The thermal stability of HRP and d-HRP at pH 6.0, measured by residual activity, was indistinguishable and showed transition midpoints at 57 degrees C, whereas the unfolding in guanidinium chloride at pH 7.0, 23 degrees C was 2-3-fold faster for d-HRP than for HRP. The results are compatible with a glycan-induced decrease in the dynamic fluctuation of the polypeptide chain.

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.

A disulfide bond between conserved cysteines in the extracellular loops of the human VIP receptor is required for binding and activation.

The importance of two highly conserved cysteines in the human vasoactive intestinal peptide receptor I (hVIPR 1) was examined. By site-directed mutagenesis each Cys residue was converted into Ala or Ser. The mutant and wild-type genes were transfected into HEK293 cells and tested for the ability to bind VIP and to activate cAMP production. Cys215-Ala/Ser and Cys285-Ala/Ser showed at least a 10-fold decrease in binding affinity and receptor potency when compared to the wild type. In contradiction to the wild-type receptor, both mutations were insensitive to dithiothreitol (DTT). The results indicate the existence of a disulfide bond between Cys215 and Cys285, which is important for stabilising the receptor in the correct conformation for ligand binding and activation.

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.

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.

High-impact poly(L/D-lactide) for fracture fixation: in vitro degradation and animal pilot study.

The impact strength of amorphous lactide copolymers can be significantly improved by blending with biodegradable rubbers. Rubber toughening of amorphous poly(85L/15D -lactide) with the copolymer poly (50/50-trimethylenecarbonate-co-epsilon-caprolactone) results in a high-impact polymer (PDLLA/P(TMC-CL)). In vitro, the PDLLA/P(TMC-CL) blend retained its tensile and impact strength for a long period of time. Up to 45 weeks, the amount of water absorbed by the blend remained very low and no significant mass loss was observed. To test the suitability for fracture fixation, in a dog study mandibular fractures were fixated with PDLLA/P(TMC-CL) bone plates and screws. Bone healing was uneventful without premature failure of the implants. Although long-term degradation studies have to be carried out, PDLLA/P(TMC-CL) seems to be promising for application in fracture fixation.

Importance of conserved cysteines in the extracellular loops of human PACAP/VIP1 receptor for ligand binding and stimulation of cAMP production.

The importance of two highly conserved cysteines in the human pituitary adenylate cyclase activating polypeptide (PACAP)/vasoactive intestinal peptide 1 (VIP1) receptor was examined. Using site-directed mutagenesis, each Cys residue was converted into Ala or Ser. The mutant and wildtype genes were transfected into HEK293 cells and tested for the ability to bind VIP and to activate cAMP production. Cys215Ala/Ser and Cys285Ala/Ser showed at least a tenfold decrease in binding affinity and receptor potency when compared to the wildtype. In contradiction to the wildtype receptor, both mutations were insensitive to dithiothreitol (DTT). The results indicate the existence of a disulfide bond between Cys215 and Cys285, which is important for stabilizing the receptor in the correct conformation for ligand binding and activation.