[A PhD completed. More insight into the origin and composition of salivary stones]. / Serie: Hora est. Meer inzicht in het ontstaan en de samenstelling van speekselstenen.

Salivary stones are hardened, stony calcifications that primarily develop in the drainage duct of a salivary gland. They can lead to obstruction of the saliva flow, resulting in swelling and pain. Since the aetiology of salivary stones remains largely unclear, this was further investigated in this PhD study. A case-control review of patient records showed that systemic diseases and lifestyle factors most likely do not play a role in their occurrence. The biochemical composition of salivary stones removed by oral-maxillofacial surgeons was examined, revealing that large salivary stones have a different inorganic composition than small salivary stones. Several salivary proteins were detected in submandibular salivary stones, including lysozyme, s-IgA, and -amylase. Clumping together of these proteins may play a role in the initial formation of salivary stones.

Letter to the Editor, "Sjögren's Disease Is Not a Clinical Risk Factor for Periodontitis".

This article is temporarily under embargo.

What is a fair price for a medicine? Establishing the main elements of a fair price based on the current policy debate.

OBJECTIVE: Unfair medicines prices have been discussed widely as an obstacle for patient access. This article aims to structure the discussion about fair pricing of medicines, analyses the elements for a fair price, and assesses its practical implications. METHODS: A systematic literature research has been undertaken and complemented by gray literature. Definitions and elements of a fair price have been extracted from the sample, categorized via a thematic and a quantitative analysis, and mirrored against the traditional framework of 'iustum pretium' (fair price). RESULTS: The most often attributes of a fair price mentioned were affordability (n = 30), followed by value and research and development (R&D) investment (n = 20). Other frequently mentioned attributes are profitability (n = 19), transparency of R&D costs (n = 18), cost-effectiveness (n = 17), and manufacturing (n = 14). Nearly all definitions present fair price as a balance between different objectives. CONCLUSIONS: Most publications stipulate that medicines are a common good and should be affordable. At the same time, most publications also propose a pricing approach based on covering costs for R&D and/or on value. Consequently, most of the attempts to clarify fair price result in a value-affordability dilemma, which does not necessarily warrant patient access. Many social health systems implement pricing regardless of the debate. This systematic review offers a set of attributes for fair price and helps refining the existing pricing and reimbursement regulations. Once complemented by empirical datapoints, it provides the basis for developing a framework for fair pricing.

Effects of transport age (14 d vs. 28 d of age) on blood total cholesterol, insulin and IGF-1 concentrations of veal calves.

The main aim of the current study was to find biomarkers of health in calves transported at different ages. The selected blood parameters were total cholesterol, insulin and IGF-1 and the longitudinal study investigated whether or not these concentrations were different between calves that were transported from the dairy farm to the veal farm at 14 d or 28 d of age. Relationships between these blood variables and health characteristics of veal calves were investigated. In a 34-wk study period, a total of 683 calves originating from 13 Dutch dairy farms were transported at an age of 14 or 28 d to 8 Dutch veal farms. Calves were blood sampled the first wk after birth (mean and SD: 4.4 ± 2.1 d), a day before transport (mean and SD: 25.8 ± 7.3 d) and in wk 2 post-transport (mean and SD: 36.7 ± 12.2 d). In these samples, insulin, IGF-1 and total cholesterol were determined and analyzed with a linear mixed model (LMM). Individual medical treatments were recorded from birth until the day of transport at the dairy farm, and from the moment of arrival at the veal farm until slaughter, and analyzed as a binary response variable (calf treated or not) with a generalized linear mixed model. Fecal (calf with or without loose or liquid manure) and navel (calves with or without swollen and inflamed navel) scores measured during a single visit in wk 2 post-transport were also analyzed as binary response variables, whereas carcass weights at slaughter age were analyzed with a LMM. Cholesterol, insulin and IGF-1 were included as covariates in the previous models to test their relationships with the likelihood of calves being medically treated, fecal and navel scores, and carcass weights. One day before transport 28 d-old calves had higher blood cholesterol (Δ = 0.40 mmol/l) and IGF-1 (Δ = 53.6 ng/ml) concentrations, and evidence of higher insulin (Δ = 12.2 µU/ml) compared with 14 d-old calves. In wk 2 post-transport, 28-d old calves had higher blood IGF-1 (Δ = 21.1 ng/ml), with evidence of higher insulin (Δ = 12.2 µU/ml) concentrations compared with 14-d old calves. Cholesterol concentration measured one day before transport and in wk 2 post-transport had a positive relationship with carcass weight at slaughter (ß = 4.8 and 7.7 kg/mmol/l, respectively). Blood cholesterol concentration in wk 2 post-transport was negatively associated with the fecal score measured at the same sampling moment (ß = -0.55/mmol/l), with the likelihood of a calf of being treated with antibiotics (ß = -0.36/mmol/l) and other medicines (ß = -0.45/mmol/l) at the veal farm. Blood IGF-1 concentration in wk 2 post-transport was negatively associated with the likelihood of a calf of being treated with antibiotics and other medicines (both ß = -0.01/ng/ml) at the veal farm, and with fecal score recorded in wk 2 post-transport (ß = -0.004/ng/ml). When looking at the blood indicators, it appeared that calves transported at 28 d of age were more developed compared with 14 d old calves, thus transport at an older age might be more beneficial for the animals. It can be concluded that both blood cholesterol and IGF-1 concentrations seemed to be valuable biomarkers of health and energy availability in veal calves.

[A PhD completed. Long-term effects of childhood cancer therapy on oral health]. / Serie: Hora est. Langetermijneffecten van de behandeling van kinderkanker op de mondgezondheid.

In recent years, the five-year survival rate for childhood cancer has increased to about 80%. However, childhood cancer therapy can have serious long-term adverse effects on general health later in life. Of survivors, 75% experience 1 or more late effects. This PhD research aimed to gain more insight into the long-term effects on oral health of childhood cancer therapy, 15 years or more after diagnosis. This study, which is part of the Dutch Childhood Cancer Survivor Study Late Effects 2 (DCCSS LATER 2 Study), showed that oral complications such as dental developmental disorders and hyposalivation occur frequently. Most important risk factors were head and neck radiotherapy of the salivary glands, (alkylating) cytostatic agents, and age at the time of the cancer diagnosis. Dentists should be aware of childhood cancer in the medical history of their patient and of the type of therapy received. Regular dental visits are an essential part of long-term follow-up care of childhood cancer survivors.

[Portrayal of dentists in films]. / Uitbeelding van tandartsen in speelfilms.

To analyze the portrayal of dentists in films, 259 films from the period 1907 - 2018 featuring one or more dentists, were systematically analyzed. A total of 333 dentists were identified, mostly of Caucasian origin (85%) and male (86%). 228 dentists depicted dental procedures, sometimes using gloves (41%), (splash) glasses (35%), and mouth masks (24%). The depicted dental procedures mainly consist of the use of pocket probes and mirrors (46%), drilling/filling (31%), and extractions (25%). Furthermore, dentists in films are relatively often involved in negative activities such as physical violence (29%) and sexual offences (18%). In 16 films (6%), dentists murdered people. Although there is no single stereotypical portrayal of dentists in films, the overall picture seems to need improvement as it is not contributing to the reputation of the dental profession.

[Hora est. The relationship between stress, salivary proteins and caries experience in children]. / Serie: Hora est. De relatie tussen stress, speekseleiwitten en cariëservaring bij kinderen.

Dental caries is a major public health problem and untreated caries has serious consequences for children. Psychosocial factors have multiple consequences, among others on the composition of saliva. Therefore, this study investigated whether stress and various salivary protein levels are associated with dental caries experience in children. The activity of the Matrix Metalloproteinases MMP-8 and MMP-9 and the total proteolytic activity in saliva turned out to be indicators for the caries experience. Salivary Alpha-Amylase seems to be a protector and was a strong indicator for caries experience. In cases where children were exposed to two different dental treatments, the level of salivary cortisol- and alpha-amylase increased, in which a distinction could be made between non-invasive and invasive treatment. The results of the study emphasise the need for further research into the way stress and salivary protein concentrations can affect the caries experience and how different dental treatments can influence the behaviour and stress levels in children.

[A challenging dental treatment of a patient with spinal muscular atrophy]. / Een uitdagende tandheelkundige behandeling van een patiënt met spinale musculaire atrofie.

After a fall from his wheelchair, a 23-year-old wheelchair-dependent patient with spinal muscular atrophy type 1 was initially seen by an emergency dentist, who repositioned and splinted the luxated teeth number 31 and 32. For stabilization, the patient was subsequently referred to a centre for special dental care. In the past, few treatments had been carried out on the patient. A jaw defect and very limited mouth opening compromised dental treatment. In addition, due to the muscle disease, the patient had respiratory and breathing problems, for which he used respiratory equipment. This case describes the importance of a multidisciplinary team in the treatment of patients with spinal muscular atrophy, and the options for performing minimally invasive dental treatment, where the priority is a painless dentition.

[The level of knowledge of master's dental students in the Netherlands and Flanders about matrix metalloproteinases]. / Kennisniveau van masterstudenten tandheelkunde in Nederland en Vlaanderen over matrixmetalloproteïnases.

Matrix metalloproteinases (MMPs) are enzymes involved in the remodelling and degradation of the extracellular matrix, which is essential for maintaining healthy oral tissues. It is therefore important for dental students to know the role of MMPs in biological processes and diseases. Using a questionnaire, a cross-sectional study was conducted among master's dental students from 3 universities in the Netherlands and Belgium. The general level of knowledge about MMPs of the 80 respondents was predominantly low (91.3%). Significant differences were observed among students from the various dental schools, with students from the University of Groningen and Ghent University scoring significantly higher than those from the Academic Centre for Dentistry in Amsterdam (ACTA). Gender was associated with a few questions on the relationship between MMPs and dentistry, with female students achieving higher scores. Improving dental curricula regarding MMPs and their role in dental processes seems warranted.

[A PhD completed. General conclusions of doctoral research into regional mouth dryness]. / Serie: Hora est. Algemene conclusies promotieonderzoek naar regionale monddroogte.

Dry mouth has a complex aetiology which makes proper diagnosis complicated. Until now, dry mouth diagnosis has mainly focused on the overall oral dryness, without taking into account regional differences within the mouth. This research showed, among other things, that there are unique patterns of oral dryness, each with its own cause. For example, patients suffering from Sjogren's syndrome mainly experienced dryness of the posterior of the palate. Patients with dry mouth due to the side effects of medication, in contrast, experienced the front part of the tongue as the driest. These findings suggest that mapping of intraoral dryness may be a useful diagnostic tool to differentiate between possible causes of dry mouth.

Use and efficacy of dry-mouth interventions in Sjögren's disease patients and possible association with perceived oral dryness and patients' discomfort.

OBJECTIVES: Sjögren's disease (SjD) patients use various interventions to relief their oral dryness. However, the use and efficacy of these interventions have only partially been evaluated. The present study aims to investigate whether there is an association between the perceived oral dryness and discomfort of SjD patients and their use of specific interventions. MATERIALS AND METHODS: A cross-sectional study was performed among SjD patients, who completed several questionnaires to assess the severity of their oral dryness and an inventory of dry-mouth interventions. The perceived efficacy of each intervention was reported on a 5-point Likert-scale. RESULTS: The questionnaires were returned by 92 SjD patients. For relief of oral dryness, they mostly used "eating fruit", "drinking tea", "moistening the lips", "drinking water, and "drinking small volumes" (> 50%). Three interventions had a frequency of use ranging from 2-6 times/day, whereas, "drinking water" and "drinking small volumes" showed higher frequencies (> 14). The highest overall efficacy (≥ 3.5) was reported for "chewing gum" and "using a mouth gel". Furthermore, various dry-mouth interventions showed significant associations with oral dryness scores and/or patients' discomfort. For example, "drinking small volumes" and "using XyliMelts" were associated with the Bother Index score. CONCLUSION: Great variation was found in the use of dry-mouth interventions by the participants and the severity of the oral dryness and/or patients' discomfort seemed to affect their choice of intervention. Notably, the mostly used interventions did not show the highest reported efficacy. CLINICAL RELEVANCE: These findings might help SjD patients and clinicians in their choice of effective dry-mouth interventions.

20-Year trends of hospitalisation among people with dementia: a region-wide retrospective cohort study from Lombardy, Italy.

OBJECTIVES: The aim of this study was to investigate the trends of hospitalisations among people with dementia, linking region-wide hospital and demographic health records. STUDY DESIGN: A retrospective cohort study was conducted using hospitalisation health records from the Lombardy region in Italy. METHODS: The study included people aged ≥65 years with a diagnosis of dementia who were hospitalised between 2002 and 2020 in Lombardy, which is the most populated region in Italy with 10 million inhabitants. Using data on resident population, this study computed rates of hospitalisation by calendar year, age, sex and cause of hospitalisation. RESULTS: In total, 340,144 hospitalised patients with dementia were included in the study. The rate of hospitalisation was 100.6 per 10,000 in 2002 and progressively decreased to 65.1 per 10,000 in 2020. The average age at hospitalisation in 2002 was 78.9 years for men and 81.8 years for women, which increased to 82.0 years and 84.2 years, respectively, in 2020. Respiratory diseases caused 10.4% of all hospitalisations in 2002 and grew steadily to 26.8% in 2020, becoming the leading cause of hospital admissions since 2017. CONCLUSIONS: Hospitalisation patterns for people with dementia have changed over the last 20 years, reflecting evolving epidemiological trends and the impact of healthcare policies. Region-wide administrative health record data analysis should be further utilised to explore the health needs of people with dementia and inform the planning, implementation and monitoring of effective prevention strategies in this population group.

[Knowledge and attitude of oral care providers in the Netherlands on skin lesions]. / Kennis en attitude van mondzorgverleners over huidafwijkingen.

To gain insight into the current knowledge of oral care providers in the Netherlands on facial skin lesions, a survey was distributed to 7,670 oral care providers. Their knowledge was tested by means of 4 multiple-choice questions and on the basis of 5 cases. The survey was completed in full by 90 respondents. The median age was 50.3 years and 62.2% were female. During dental check-ups, 55.6% always examined the face and 41.1% sometimes did so. Compared to the group 41 years old and older, the group 21-40 years of age alerted their patients more often to skin lesions (p = 0.017), was more afraid a specialist would find the referral useless (p < 0.001) and was more in need of a guideline (p = 0.049). The respondents scored 1.90 out of 4 correct answers to the knowledge questions. On the case studies, they scored 1.46 out of 5 for the correct diagnosis, 3.48 out of 5 for the correct choice of policy and 1.01 out of 5 for the combination correct diagnosis and correct policy. The total score was 2.91 out of 9. The results indicate that knowledge on aspects of skin lesions is limited and additional training and the availability of a guideline are necessary.

Uptake and incorporation of Al, Cr, V, Zn and Mo in hematite: Competition, synergies and influence on structural properties.

This study investigated multiple (di-, tri- and tetra-)incorporation of selected minor and trace elements (Al3+, Cr3+, V3-5+, Zn2+, Mo6+ and As5+) into hematite. The purpose was to improve understanding of how hematite may control trace element mobility in the environment, and how physical and chemical properties of hematite are impacted by multi-element incorporation at x/Fe molar ratios of up to 10%. Simultaneous structural incorporation of Al±Cr±V±Zn into hematite was achieved, with both synergistic and antagonistic effects occurring between certain element combinations. Cr+Al had synergistic effects on their co-incorporation, while V negatively affected Al incorporation, and both V and Zn negatively affected Cr incorporation. In contrast, Mo was minimally associated with hematite, and As prevented hematite formation completely. X-ray diffraction indicated contraction and expansion of the hematite unit-cell upon substitution was related to the ionic radius of the substituting element in single-element samples, while V predominantly controlled the direction of deviation in multi-element samples. X-ray absorption near-edge structure spectroscopy indicated V was present as a mixture of V3+-V5+, with a higher average V oxidation state associated with multi-element samples. Results provide new insights into trace element geochemistry within hematite, and highlight the importance of multi-element studies to better understand natural and anthropogenic systems.

Genetics of rearing success in four pure laying hen lines during the first 17 weeks of age.

This study aimed to investigate the genetics of rearing success (RS) in laying hens. Four rearing traits: clutch size (CS), first week mortality (FWM), rearing abnormalities (RA), and natural death (ND), were included as factors determining RS. Pedigree, genotypic, and phenotypic records of 4 purebred genetic lines of White Leghorn layers were available for 23,000 rearing batches obtained between 2010 and 2020. FWM and ND showed little or no variation amongst the 4 genetic lines over the years 2010-2020, whereas an increase was observed for CS and a decrease for RA. To determine whether these traits were heritable, genetic parameters for each trait were estimated, using a Linear Mixed Model. Heritabilities within lines were low (0.05-0.19 for CS, 0.01-0.04 for FWM, 0.02-0.06 for RA, 0.02-0.04 for ND, and 0.01-0.07 for RS). Additionally, genome wide association study was done to scan the genomes of the breeders to reveal single nucleotide polymorphisms (SNPs) associated with these traits. Manhattan plots indicated the existence of 12 different SNPs having a significant effect on RS. Thus, the identified SNPs will increase the understanding of the genetics of RS in laying hens.

[Oral health of recreational ecstasy-users]. / Mondgezondheid bij recreatief ecstasygebruik.

In a cross-sectional study, dental records of 149 individuals visiting an Academic Dental Clinic in Amsterdam who reported recreational ecstasy use, defined as no more than twice a week, were systematically analyzed and compared to a group of age- and sex-matched non-drug-users. The parameters retrieved from the dental records were decayed, missing, and filled permanent teeth-index (DMFT-index), number of endodontically treated teeth, presence of active caries lesions, periodontitis, tooth wear, xerostomia, and self-reported use of oral hygiene devices. Periodontitis, active caries lesions, and xerostomia were statistically significantly more present in ecstasy-users. Ecstasy-users brush their teeth significantly less frequent per day than non-recreational-drug-users. There were no significant differences in DMFT-index and in the devices used for brushing and interdental cleaning, and frequency of use of these interdental devices between both groups. We conclude that periodontitis, active caries lesions, and xerostomia, are more frequently present in recreational ecstasy-users compared to age- and sex-matched non-users.

Knowledge of diagnosis and management of selected oral mucosal lesions among dentists in The Netherlands.

BACKGROUND: Knowledge of oral mucosal lesions (OMLs) among dentists is relevant in diagnosing potentially malignant diseases and oral cancer at an early stage. The aim of this survey was to explore dentists' knowledge about OMLs. MATERIAL AND METHODS: Respondents to a web-based questionnaire, containing 11 clinical vignettes representing patients with various OMLs, provided a (differential) diagnosis and management for each. Information about demographics and clinical experience of the participants was acquired as well. Descriptive statistics were performed and T-tests were used to test for significant (p<0.05) differences in mean scores for correct diagnosis and management between subgroups based on demographic variables. RESULTS: Forty-four of 500 invited dentists completed the questionnaire. For (potentially) malignant OMLs, the number of correct diagnoses ranged from 14 to 93%, whilst the number of correct management decisions ranged from 43 to 86%. For benign OMLs, the number of correct diagnoses and management decisions ranged from 32 to 100% and 9 to 48%, respectively. For 11 clinical vignettes, mean scores for correct diagnosis, correct management and correct diagnosis and management were respectively 7.2 (±1.8), 5.7 (±1.5), and 3.8 (±1.7). CONCLUSIONS: The results show that dentists in the Netherlands do not have sufficient knowledge to accurately diagnose some OMLs and to select a correct management. This may result in over-referral of benign OMLs and under-referral for (potentially) malignant OMLs. Clinical guidelines, that include standardized criteria for referral, and continuing education, may improve dentists' ability to correctly diagnose and accurately manage OMLs.

Changes in body composition and energetic efficiency in response to growth curve and dietary energy-to-protein ratio in broiler breeders.

Body composition plays an important role in reproduction in broiler breeders. The aim of this study was to evaluate the dynamics in body composition and energetic efficiency in broiler breeders, using different dietary strategies. About 1,536-day-old pullets were randomly allotted to 24 pens in a 2 × 4 factorial design with 2 growth curves (standard or elevated (+15%)) and 4 diets, with a step-wise increment in energy (96, 100, 104, and 108% apparent metabolizable energy nitrogen corrected [AMEn]) fed on a pair-gain basis. Body composition was determined at 10 time points from 0 to 60 wk of age. Body protein mass was linearly related to body weight (BW) in growing breeders, which can be expressed as -6.4+0.184*BW (R2 = 0.99; P < 0.001). Body fat mass was exponentially related to BW in growing breeders, which can be expressed as -42.2+50.8*1.0006BW (R2 = 0.98; P < 0.001). A higher energy-to-protein ratio resulted in higher body fat mass at the same BW (P < 0.001). Sexual maturation was related to body protein mass at 21 wk of age, where each 100 g of body protein mass extra advanced sexual maturation by 5.4 d (R2 = 0.83). Estimates of energetic efficiency for growth (kg) and egg production (ke) appeared not constant, but varied with age in a quadratic manner between 0.27 and 0.54 for kg and between 0.28 and 0.56 for ke. The quadratic relationship could be expressed as kg=0.408-0.0319*Age+0.00181*Age2 (R2 = 0.72; P < 0.001) and ke=-0.211+0.034*Age-0.00042*Age2 (R2 = 0.46; P < 0.001). Body protein mass in broiler breeders is tightly regulated and mainly depended on BW and seems to be the main determinant for sexual maturation. Body fat mass is exponentially related to BW, where an increase in dietary energy-to-protein ratio results in a higher body fat mass. Treatments had minimal effects on estimated energetic efficiencies in breeders.

Salivary film thickness and MUC5B levels at various intra-oral surfaces.

OBJECTIVES: In this study, we investigated the salivary film thickness and the MUC5B levels at various intra-oral locations in healthy volunteers, with a focus on the palate. Besides, measurements of the palatal surface area were included to explore the possible relationships between the palatal surface area and the palatal salivary film and MUC5B levels. MATERIALS AND METHODS: The salivary film thickness was determined using filter strips, which were pressed to the mucosal surfaces of five different intra-oral locations; conductance was then analysed using a Periotron. After elution of the strips, the MUC5B levels at various intra-oral locations were determined using ELISA. The palatal surface area was measured using an intra-oral scanner. The surface area was subsequently calculated using the software. RESULTS: The anterior tongue had the thickest salivary film and also the highest levels of MUC5B, while the anterior palate had the thinnest salivary film and lowest MUC5B levels. There was no association between the palatal surface area and the salivary film thickness of the palate. CONCLUSION: The salivary film and MUC5B levels are unequally distributed over the intra-oral regions of the soft tissues. The lack of association between the palatal surface area and the salivary film thickness indicates that a larger surface area is not associated with a relative thinner palatal salivary film. CLINICAL RELEVANCE: The results of the current study increase our understanding of saliva distribution in the oral cavity and could be used as reference values for future studies.