[A PhD completed. Oral manifestations in inflammatory bowel diseases]. / Serie: Hora est. Orale manifestaties van inflammatoire darmziekten.

Crohn's disease and ulcerative colitis are chronic inflammatory diseases of the gastrointestinal tract. In addition to bowel symptoms, patients may also have oral manifestations. This thesis investigated potential associations between disease activity in the gut, oral health, salivary gland function, and saliva composition. Patients with Crohn's disease had a significantly higher DMFT index, but showed no difference in periodontal diseases compared to a healthy control group. The saliva composition in patients with active bowel disease differed from that in patients with inactive bowel disease, suggesting that saliva analysis could potentially be used in the future to determine the degree and severity of bowel disease. The knowledge of gastroenterologists and dentists regarding oral manifestations of bowel diseases was found to be limited. Gastroenterologists and dentists valued interdisciplinary patient consultation as very useful, but the frequency of consultation was considered insufficient.

[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.

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.

Effects of a communication training for oncologists on early addressing palliative and end-of-life care in advanced cancer care (PALLI-COM): a randomized, controlled trial.

INTRODUCTION: In advanced cancer care, early communication about palliative care (PC) and end-of-life (EoL)-related issues is recommended, but is often impeded by physicians' communication insecurities. We investigated the effect of a newly developed compact communication skills training 'PALLI-COM' on oncologists' competencies to early address PC/EoL-related issues. MATERIALS AND METHODS: We conducted a randomized, controlled trial (RCT) with an intervention group (IG; 2 × 90 min training) and a wait list control group (CG) at five sites. At two assessment points, participating oncologists led videotaped medical consultations with simulated patients (SPs) via a privacy compliant video conference platform. SPs were represented by trained actors. The taped conversations were rated for primary outcome (communication skills assessed by adapted COM-ON-checklist and COM-ON-coaching rating scales) by raters blinded for study group. Secondary outcomes included oncologists' self-reported communication skills (Self-Efficacy in Palliative Care Scale, Thanatophobia-Scale, Communication about End of Life Survey, study-specific items) as well as external rating of the SPs. Univariate analyses of covariance with baseline adjustment were used to analyze intervention effects. RESULTS: A total of 141 oncologists [age: mean (standard deviation) = 32.7 (6.3) years, 60% female (nIG = 73, nCG = 68)] participated. Following intervention, the IG showed significantly more improvement in four out of five assessed communication skills: 'reacting to emotions and showing empathy', 'pointing out opportunities and giving hope', 'addressing the EoL' and 'explaining the concept of PC'. IG participants also improved more than CG participants in almost all secondary outcomes assessed by participants and SPs: oncologists' self-efficacy, attitudes towards caring for terminally ill patients, communication strategies and confidence in dealing with PC/EoL-related issues as well as communication quality from the SPs' perspective. CONCLUSION: Findings indicate that the compact communication skills training PALLI-COM increases oncologists' competencies in early addressing PC/EoL-related issues from different perspectives. Implementation in routine oncology residency might improve advanced cancer care by strengthening these communication skills.

[Human papillomavirus vaccination available for boys also; information for oral healthcare providers]. / Humaan papillomavirus-vaccinatie nu ook beschikbaar voor jongens: informatie voor mondzorgverleners.

Recently, the Dutch National Immunization Programme has started to offer the human papillomavirus (HPV) vaccination to boys as well as girls from the age of 10. The vaccine protects against long-term HPV infection, which can lead to cervical, anogenital and oropharyngeal cancer. Besides malignant disorders, a HPV infection can also lead to certain disorders of the skin and oral cavity. Since the national HPV vaccination campaign has probably resulted in more awareness among patients about the relation between HPV and oropharyngeal cancer, patients may consult oral healthcare professionals with questions about HPV infection. Oral healthcare professionals are thus able to play a role in preventing HPV related disorders by counseling their patients on HPV. They can also contribute to early diagnosis of HPV related oral and oropharyngeal disorder, although the possibility of detecting oropharyngeal cancer during routine dental examination  is limited.

[Knowledge of Dutch dentists regarding HPV associated cancer of the oropharynx]. / Kennis van Nederlandse tandartsen over orofarynxkanker veroorzaakt door het humaan papillomavirus.

Worldwide and also in the Netherlands there is an increasing human papillomavirus (HPV)-attributable oropharyngeal cancer incidence. This type of cancer is more common at a younger age than the classical oropharyngeal cancer, which is usually caused by smoking and excessive drinking. Most often, the tumor occurs in the tonsils and at the base of the tongue. This study explored the level of knowledge of dentists about oropharyngeal cancer, its association with the human papillomavirus and their willingness to play a role in prevention. 7.364 digital questionnaires were sent to oral health-care providers and data from 607 dentists was analyzed. 48% of knowledge questions were answered correctly by more than half of the respondents. Significantly more female caregivers were aware of the relationship between HPV and oropharyngeal cancer and the availability of an HPV vaccine. Respondents considered it important that the relationship between HPV and oropharyngeal cancer is discussed with patients and that a protocol is developed that is useful in screening for mouth and throat cancer.

[What are the differences between the various covid-19 vaccines?] / Wat zijn de verschillen tussen diverse vaccins tegen COVID-19?

The coronavirus pandemic is caused by the SARS-CoV-2. Vaccination appears to offer the way out of this pandemic. Vaccines against this virus make use of the SARS-CoV-2's spike protein, an essential protein on the surface of the virus that it uses to attach itself to the host cells. In viral vector vaccines (AstraZeneca, Sputnik, Johnson & Johnson) the gene for the spike protein is introduced into an adenovirus. Following vaccination, the modified adenovirus will infect cells of the host, which will subsequently start to produce the spike protein, causing an immune response. RNA vaccines (Pfizer, Moderna) only introduce messenger RNA for the spike protein into host cells, which the messenger RNA uses to produce spike protein. Viral vector vaccines and RNA vaccines are not only faster to develop and safer to produce than traditional vaccines, they are also easier to modify to new viruses and virus variants. The latter may be of great importance for future pandemics.

[Does a heart transplant affect oral health?] / Beïnvloedt een harttransplantatie de mondgezondheid?

A heart transplant procedure is performed on patients who have an end-stage heart disease (severe failure) for whom no other treatment is left. Patients need to take immunosuppressive drugs for the rest of their lives to prevent the rejection of a transplanted heart. A recent overview of scientific literature shows a higher risk of gingival hyperplasia, periodontal conditions, the presence of Candida species and oral malignancies compared to healthy individuals. The association between a heart transplant and dental caries is unclear. A frequent periodical dental check and professional dental cleaning is recommended for heart transplant patients.

[Effects of krokodil (desomorphine) use on oral health]. / Effecten van gebruik drug 'krokodil' (desomorfine) op de mondgezondheid.

A 52-year-old man with a history of krokodil (desomorphine) use was admitted to the department of oral and maxillofacial surgery with drug intoxication and severe pain in his jaw. During clinical and radiological examination, several sites of exposed necrotic bone with purulent discharge were seen. In krokodil-using patients osteonecrosis of the jaw is a frequently occurring manifestation. Other oral aspects associated with the use of krokodil include mucosal changes, a high risk of caries and periodontitis. Systemic effects can interfere with dental and oral and maxillofacial treatment. Treatment consists of sequestrectomy of the necrotic bone under general anaesthesia. The clinical picture of osteonecrosis in krokodil users is similar to cases of 'phossy jaw' and Medication Related Osteonecrosis of the Jaw (MRONJ).

Oral health complications after a heart transplant: a review.

Background Heart transplants have become a successful treatment for some cardiovascular diseases. To prevent rejection of the transplanted heart, patients have to take immunosuppressive medication.Aims The aims of this study were to identify and review oral health complications after heart transplantation.Methods The electronic database PubMed was searched for relevant articles. The search yielded 332 papers, of which 24 matched the criteria for this review.Results Gingival hyperplasia was observed in 8.3-67% of the patients. Heart transplant patients who received professional periodontal treatment starting six months after transplantation showed significantly better scores on the Gingival Index (GI) and gingival hyperplasia. In comparison to a control group, heart transplant patients did not differ significantly in the DMF(T) index. The incidence of fungal infection in patients receiving a heart transplant varied between 10% and 25%. Heart transplant patients had a 4.3 times higher chance of developing oral cancer.Conclusion Patients who underwent a heart transplant and subsequently used immunosuppressive medicines appear to have a higher risk of gingival hyperplasia, periodontal conditions, the presence of Candida species and oral malignancies, in comparison to healthy individuals. The association between heart transplants and dental caries was unclear. It is recommended that heart transplant patients receive frequent oral examination and professional dental cleaning.

Effects of dietary organic minerals, fish oil, and hydrolyzed collagen on growth performance and tibia characteristics of broiler chickens.

Nutrition is a crucial factor for growth and bone development in broiler chickens. Adjustments in dietary ingredients might affect bone development and consequently locomotion related problems. This study was designed to evaluate effects of dietary organic minerals (ORM), fish oil (FISH), and hydrolyzed collagen (COL) on growth performance and tibia characteristics of broiler chickens. A total of three hundred eighty four 1-day-old Ross 308 male broiler chickens were used in a complete randomized block design with 4 diet groups and 8 replicates per diet group. In the ORM diet, the inorganic macro and trace minerals were replaced by their organic varieties. In the FISH diet, palm oil and soybean oil were partly replaced by FISH. In the COL diet, soybean meal was partly replaced by COL. Results showed that the ORM and COL diet groups reached a higher body weight (BW) at 42 D of age than the FISH diet group, whereas the control group was in between. The feed conversion ratio between day 1 and 42 was lower in the ORM and COL diet groups than in both other diet groups. On day 28, 35, and 42, gait score (GS), Varus Valgus deformity, tibia length (TL), thickness, femoral and metatarsal head thickness (THT), mineral content (TMC), mineral density (TMD), breaking strength (TBS), stiffness (TSF), and energy to fracture (TEF) were measured (n = 3/replicate). The ORM diet group had higher TL at day 42, higher THT at day 28, higher TMC at day 42, higher TMD at day 28, 35, and 42, higher TBS at day 42, higher TSF at day 35 and 42, and higher TEF at day 42 compared to the FISH diet group, with the COL and control diet groups in between. It can be concluded that replacing dietary inorganic macro and trace minerals by their organic varieties seems to stimulate tibia dimensions, strength, and mineral content of broiler chickens. On the contrary, FISH appears to negatively affect tibia characteristics.

Biochemical composition of salivary stones in relation to stone- and patient-related factors.

BACKGROUND: Salivary stones are calcified structures most often found in the main duct of the submandibular or parotid salivary gland. They contain of a core surrounded by laminated layers of organic and inorganic material. MATERIAL AND METHODS: Submandibular and parotid sialoliths (n=155) were collected at the department of Oral and Maxillofacial surgery of a general hospital between February 1982 and September 2012. The weight of the sialoliths was determined and the consistency was subjectively classified. Subsequently, the biochemical composition of the stones was determined by wet chemical methods or FT-IR spectrometry. Age and gender of the patients were retrieved from their medical records. Data were statistically analyzed using Fisher's exact tests. RESULTS: Sialoliths are mainly composed of inorganic material. Carbonate apatite was identified in 99% of the stones, phosphate in 88%, calcium in 87%, magnesium in 68%, struvite in 44%, oxalate in 38% and carbonate in 35%. Solid salivary stones contain more frequently struvite than stones with a soft consistency (p=0.05). Larger stones (>100mg) contain more frequently carbonate (p=0.05). Stones from older patients (≥38years) showed an almost significant trend towards more frequent presence of phosphate (p=0.083). CONCLUSIONS: The biochemical composition of submandibular and parotid sialoliths is related to stone-related factors, probably to age but not to the gender of the patient.

[Oral manifestations of Crohn's disease]. / Orale manifestaties van de ziekte van Crohn.

Gastrointestinal symptoms are predominant in Crohn's disease. Oral manifestations may also occur. The prevalence of oral manifestations varies between 0.5% and 37%. The manifestations may coincide with or precede gastrointestinal symptoms, and can be subdivided into specific and non-specific lesions. In most patients, lesions are asymptomatic but some patients experience serious discomfort. Oral manifestations can be classified as specific lesions, such as diffuse lip and buccal swelling and cobblestones, and non-specific lesions, such as aphthous ulcers, pyostomatitis vegetans, caries, gingivitis and periodontitis. In many patients, these oral symptoms do not cause pain or discomfort and do not require treatment. For patients who do experience discomfort, pain caused by aphthous ulcers, for example, can be relieved with a lidocaine solution or a 0.1% dexamethasone gel, and corticosteroids can be used to treat pain caused by ulceration or cobblestoning. It is advisable in complex cases to consult the patient's gastroenterologist.

Gastrointestinal diseases and their oro-dental manifestations: Part 2: Ulcerative colitis.

Ulcerative colitis is a rather common inflammatory bowel disease, especially in the industrialised world. A limited number of studies have reported the prevalence of oral signs and symptoms in these patients, and widely varying prevalence rates have been reported ranging from 2 to 34%. Pyostomatitis vegetans is the most pathognomonic oral sign but also other abnormalities as oral ulcerations, caries and periodontitis are more often seen in patients with ulcerative colitis. In this review we describe the oral manifestations of ulcerative colitis and their potential dental implications.

Gastrointestinal diseases and their oro-dental manifestations: Part 1: Crohn's disease.

Widely varying prevalence rates of oral lesions in patients with Crohn's disease have been reported, ranging from 0.5% to 37%. These manifestations may coincide with or precede intestinal symptoms. Oral manifestations can be classified as specific lesions, when macroscopic examination shows similar changes to those observed endoscopically in the intestine, and non-specific lesions including aphthous ulcerations. The most frequently observed oral lesions are oedema, ulcers and hyperplastic lesions on the buccal mucosa. In most patients these lesions are asymptomatic, however, some patients may experience discomfort. In this review we describe the most relevant oro-dental manifestations observed in patients with Crohn's disease and discuss the potential implications for oro-dental management.

Effects of feed access after hatch and inclusion of fish oil and medium chain fatty acids in a pre-starter diet on broiler chicken growth performance and humoral immunity.

Delayed feed and water access is known to impair growth performance of day old broiler chickens. Although effects of feed access on growth performance and immune function of broilers have been examined before, effects of dietary composition and its potential interaction with feed access are hardly investigated. This experiment aimed to determine whether moment of first feed and water access after hatch and pre-starter composition (0 to 7 days) affect growth rate and humoral immune function in broiler chickens. Direct fed chickens received feed and water directly after placement in the grow-out facility, whilst delayed fed chickens only after 48 h. Direct and delayed fed chickens received a control pre-starter diet, or a diet containing medium chain fatty acids (MCFA) or fish oil. At 21 days, chickens were immunized by injection of sheep red blood cells. The mortality rate depended on an interaction between feed access and pre-starter composition (P=0.014). Chickens with direct feed access fed the control pre-starter diet had a higher risk for mortality than chickens with delayed feed access fed the control pre-starter diet (16.4% v. 4.2%) whereas the other treatment groups were in-between. BW gain and feed intake till 25 days in direct fed chickens were higher compared with delayed fed chickens, whilst gain to feed ratio was lower. Within the direct fed chickens, the control pre-starter diet resulted in the highest BW at 28 days and the MCFA pre-starter diet the lowest (Δ=2.4%), whereas this was opposite for delayed fed chickens (Δ=3.0%; P=0.033). Provision of MCFA resulted in a 4.6% higher BW gain and a higher gain to feed ratio compared with other pre-starter diets, but only during the period it was provided (2 to 7 days). Minor treatment effects were found for humoral immune response by measuring immunoglobulins, agglutination titers, interferon gamma (IFN- γ ), and complement activity. Concluding, current inclusion levels of fish oil (5 g/kg) and MCFA (30 g/kg) in the pre-starter diet appear to have limited (carryover) effects on growth and development, as well as on humoral immune function.

FOXO3a loss is a frequent early event in high-grade pelvic serous carcinogenesis.

Serous ovarian carcinoma is the most lethal gynecological malignancy in Western countries. The molecular events that underlie the development of the disease have been elusive for many years. The recent identification of the fallopian tube secretory epithelial cells (FTSECs) as the cell-of-origin for most cases of this disease has led to studies aimed at elucidating new candidate therapeutic pathways through profiling of normal FTSECs and serous carcinomas. Here we describe the results of transcriptional profiles that identify the loss of the tumor suppressive transcription factor FOXO3a in a vast majority of high-grade serous ovarian carcinomas. We show that FOXO3a loss is a hallmark of the earliest stages of serous carcinogenesis and occurs both at the DNA, RNA and protein levels. We describe several mechanisms responsible for FOXO3a inactivity, including chromosomal deletion (chromosome 6q21), upregulation of miRNA-182 and destabilization by activated PI3K and MEK. The identification of pathways involved in the pathogenesis of ovarian cancer can advance the management of this disease from being dependant on surgery and cytotoxic chemotherapy alone to the era of targeted therapy. Our data strongly suggest FOXO3a as a possible target for clinical intervention.

Exposure of fallopian tube epithelium to follicular fluid mimics carcinogenic changes in precursor lesions of serous papillary carcinoma.

OBJECTIVES: Ovulation-related inflammation is suspected to have a causal role in ovarian carcinogenesis, but there are no human models to study the molecular pathways. Our aim is to develop such an ex-vivo model based on human fallopian tube (FT) epithelium exposed to human follicular fluid (FF). METHODS: FT epithelium was dissociated from normal surgical specimens. FF was obtained from donors undergoing in-vitro fertilization. The cells were cultured on collagen-coated Transwells and incubated with FF for various periods of time. The transcriptomic changes resulting from FF treatment were profiled using Affymetrix expression arrays. Specific characteristics of the FT pre-cancerous lesions were studied using immunohistochemistry, immunofluorescence, RT-PCR and XTT assay. RESULTS: We show that FF exposure causes up-regulation of inflammatory and DNA repair pathways. Double stranded DNA breaks are induced. There is a minor increase in cell proliferation. TP53, which is the hallmark of the precursor lesion in-vivo, is accumulated. Levels of expression and secretion of Interleukin-8 are significantly increased. CONCLUSIONS: Our model addresses the main non-genetic risk factor for ovarian cancer, namely the impact of ovulation. This study demonstrates the biological implications of in-vitro exposure of human FT epithelial cells to FF. The model replicates elements characterizing the precursor lesions of ovarian cancer, and warrants further investigation of the linkage between repeated exposure to ovulation-related damage and accumulation of neoplastic changes.

Financing public health in europe.

AIM: The aim of this study was to ascertain the levels and mechanisms of funding public health in Europe. METHODS: A review of published and unpublished documents and expenditure data was undertaken. RESULTS: Expenditure on public health in Europe is difficult to determine, but data from national health accounts suggest that it differs greatly across countries, both as a percentage of total health expenditure and per capita. Better data are urgently needed, given that a lack of sustainable, long-term funding may be the most significant barrier to public health programmes and interventions in Europe. CONCLUSIONS: In view of the current economic crisis, it will be essential to safeguard financing for public health and to put it on a more sustainable basis.

[Hindering the immune system by tumours in the head and neck area]. / Remming van het immuunsysteem door tumoren in het hoofd-halsgebied.

Head and neck tumours possess several mechanisms to hinder an appropriate immune response against the tumour cell. In the first place, the tumour cells attempt to suppress the presentation of tumour-associated antigens to the cells of the immune system. Tumours also have a negative effect on the surface structures of the efferent blood vessel epithelium, thereby inhibiting the recruitment of immune cells. In addition, proteins are secreted capable of inactivating immune cells. These immunosuppressive activities of the tumour result in a deterioration of life expectancy. Several experimental methods to improve the immune response of the patient against tumour cells are currently being explored.