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Objectives In spite of extensive research, no effective treatment of primary burning mouth syndrome ( BMS) still exists. The aim of this study was to determine the impact of informative intervention/reassurance on pain perception and quality of life in patients with primary BMS. Materials and Methods Informative intervention/reassurance was undertaken in 28 patients diagnosed with primary BMS. Patients received information about all aspects of BMS verbally and in an informative leaflet. Numerical scale (0-10), Pain Catastrophizing Scale and Oral Health Impact Profile-14 ( OHIP-14) were used to assess pain intensity, pain perception, and quality of life before the intervention and 6 months after. No other treatment was given to the patients. Results Significant reduction in symptom intensity, pain catastrophizing along with positive increase in the quality of life compared with baseline, was observed on a follow-up examination 6 months after the informative intervention ( P < 0.001). Conclusions The results of this study confirm that objective informing/reassurance of patients with primary BMS can result in decreased catastrophizing and improvement in the quality of life. By eliminating/changing negative patterns of behavior, a reduction in symptoms comparable with pharmacological treatment can be achieved. [ABSTRACT FROM AUTHOR]

Drugs may be defined as substances used in the diagnosis, treatment, or prevention of a disease or as a component of a medication or alternatively as chemical substances, such as a narcotic or hallucinogen, affecting the central nervous system, causing changes in behavior and often addiction. Orofacial drug-related adverse reactions may present initially to the dental surgeon or doctor and require specialist opinion. Due to the complexity of clinical presentation including symptoms (pain, dysgeusia, xerostomia and dysaesthesia) and signs (mucosal and bone pathology) diagnostic problems are common and a detailed prescribed and non-prescribed medication history invalid. New therapeutic interventions are continually introduced across Europe and health care practitioners should be vigilant for unreported oro-facial adverse reactions and be able to access the local reporting mechanism. The benefits of the drug prescribed weighed against the risk from the oro-facial adverse reaction will determine if drug cessation is appropriate. This paper aims to update practitioners on the spectrum of drug-related oro-facial disease, review factors to be elicited from the drug history, focus on newly introduced drugs and their, in some cases devastating, oro-facial adverse effects and discuss management options. [ABSTRACT FROM AUTHOR]

Purpose: To provide evidence-based recommendations for prevention and management of osteoradionecrosis (ORN) of the jaw secondary to head and neck radiation therapy in patients with cancer., Methods: The International Society of Oral Oncology-Multinational Association for Supportive Care in Cancer (ISOO-MASCC) and ASCO convened a multidisciplinary Expert Panel to evaluate the evidence and formulate recommendations. PubMed, EMBASE, and Cochrane Library databases were searched for randomized controlled trials and observational studies, published between January 1, 2009, and December 1, 2023. The guideline also incorporated systematic reviews conducted by ISOO-MASCC, which included studies published from January 1, 1990, through December 31, 2008., Results: A total of 1,539 publications were initially identified. There were 487 duplicate publications, resulting in 1,052 studies screened by abstract, 104 screened by full text, and 80 included for systematic review evaluation., Recommendations: Due to limitations of available evidence, the guideline relied on informal consensus for some recommendations. Recommendations that were deemed evidence-based with strong evidence by the Expert Panel were those pertaining to best practices in prevention of ORN and surgical management. No recommendation was possible for the utilization of leukocyte- and platelet-rich fibrin or photobiomodulation for prevention of ORN. The use of hyperbaric oxygen in prevention and management of ORN remains largely unjustified, with limited evidence to support its practice.Additional information is available at www.asco.org/head-neck-cancer-guidelines.

Objectives: Opiorphin is an analgesic peptide released by salivary glands and capsaicin an agonist of TRPV1 receptors eliciting burning sensations. The primary objective of this study was to assess opiorphin release after stimulation of the tongue by capsaicin (STC). The secondary objectives were to compare opiorphin release after STC in 3 groups of subjects [healthy (CTRL), Burning Mouth Syndrome (BMS), painful Temporomandibular disorders (TMDp)] and pain evoked by STC in these 3 groups., Materials and Methods: Salivary opiorphin was assessed with high-performance liquid chromatography at 3 different time points (baseline, after 5 min and 20 min of STC). Pain was self-reported on a (0-10) numeric rating scale., Results: Three groups (N = 16) of adults were recruited at the Clinical Hospital Centre and School of Dental Medicine in Zagreb. Opiorphin levels were higher (1) in TMDp compared to CTRL in 1st (2.23 ± 1.72 pg/ul vs. 0.67 ± 0.44 pg/ul, p = 0.002) and 3rd sampling (2.44 ± 2.01 pg/ul vs. 0.74 ± 0.52 pg/ul, p = 0.020) and (2) within BMS group at 3rd sampling vs. baseline (p < 0.025). Pain scores were higher in BMS compared to TMDp (p < 0.025) and CTRL (p < 0.025)., Conclusion: This study evidenced (1) a differential basal amount of opiorphin in two pain conditions and control subjects (2) a differential kinetic of release of opiorphin after STC in CTRL, BMS and TMDp (3) a differential pain perception after STC in BMS and TMDp vs. CTRL, which can provide a readout for animal models., Clinical Relevance: The specific regulation of opiorphin release in patients with orofacial painful conditions provides valuable insights for clinicians and researchers in physiology and pathology and encourages further research in this area., Trial Registration: ClinicalTrials.gov NCT04694274. Registered on 01/05/2021., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Some studies have shown burning mouth syndrome (BMS) as comorbid psychosocial and psychiatric disorders, and as well, pointed at stress as a major risk factor., Objective: The aim of this meta-analysis was to answer the following question: 'Is there an association between BMS and stress, compared to healthy controls?', Methods: Two reviewers searched for the effect of stress in BMS and published on five main databases and three from the grey literature. Various questionnaires and biomarkers were analysed. Of the 2489 selected articles, 30 met the inclusion criteria. Studies englobed questionnaires, such as Perceived Stress Questionnaire, Lipp Stress Symptoms Inventory, Holmes-Rahe scale, Depression, Anxiety, and Stress Scale (DASS-21), Recent Experience Test; and various biomarkers, such as cortisol, opiorphin, IgA, α-amylase and interleukins., Results: In all studies with questionnaires, stress was significantly increased in the BMS group vs. control. Patients with BMS presented 25.73% higher cortisol levels, 28.17% higher IgA levels and 40.62% higher α-amylase levels than controls. Meta-analysis found that BMS subjects presented 3.01 nmoL/L [0.53; 5.50] higher cortisol levels, 84.35 kU/L [15.00; 153.71] higher α-amylase levels, 29.25 mg/mL [9.86; 48.64] higher IgA levels and 258.59 pg/mL [59.24; 457.94] higher IL-8 levels than control. No differences were found for opiorphin concentration in ng/mL [-0.96; 2.53]. For interleukins, no differences were founded for IL-1 β, IL-2, IL-4, IL-6, IL-8, IL-10 and TNF-α., Conclusion: Based on the available evidence, this meta-analysis suggests more stress factors in questionnaire-based studies, and higher levels of cortisol, α-amylase, IgA and IL-8 biomarkers in BMS subjects than controls., (© 2023 The Authors. Journal of Oral Rehabilitation published by John Wiley & Sons Ltd.)

The aim of this meta-analysis was to answer the following question: "Are there any differences in opiorphin biomarker concentrations between different orofacial conditions and controls?". Two reviewers searched for observational studies that evaluated the levels of opiorphin in orofacial conditions, annotated in seven main databases and three that compile gray literature. Of the 443 articles obtained initially, 8 met the inclusion criteria for quantitative analyses. Relative percentages showed a mean 24.1% higher opiorphin concentration in chronic conditions (Burning Mouth Syndrome, Oral Potentially Malignant Diseases and Temporomandibular Disorder) compared to controls; 33.2% higher opiorphin in sustained pain (Symptomatic Irreversible Pulpitis, Symptomatic Apical Periodontitis, Painful Oral Soft-tissue conditions); and 21.7% higher opiorphin after stimuli (Corneal Foreign Body, Capsaicin). Meta-analysis revealed a standardized mean difference of 0.62 [0.02, 1.22] in the absolute concentration of opiorphin in saliva for the chronic group compared to the control. The analogous values for the sustained group and the stimulated group were 2.24 [0.34, 4.14] and 0.43 [0.00, 0.85], respectively. No differences in opiorphin levels were found for 'after Local Anesthesia before Tooth Extraction' or for apicoectomy. Based on the available evidence, in general, a statistically higher level of opiorphin is found in orofacial conditions. Salivary opiorphin levels are elevated in chronic, persisted and acute pain conditions, presumably reflecting a physiological homeostatic adaptative response to different conditions such as stress or pain. Salivary opiorphin might therefore be used as a valuable biomarker in several oral disorders., (© 2023. Springer Nature Limited.)

The success rate of regenerative medicine largely depends on the type of stem cells applied in such procedures. Consequently, to achieve the needed level for clinical standardization, we need to investigate the viability of accessible sources with sufficient quantity of cells. Since the oral region partly originates from the neural crest, which naturally develops in niche with decreased levels of oxygen, the main goal of this work was to test if human oral mucosa stem cells (hOMSC) might be used to treat neurons damaged by anoxia. Here we show that hOMSC are more resistant to anoxia than human induced pluripotent stem cells and that they secrete BDNF, GDNF, VEGF and NGF. When hOMSC were added to human neurons damaged by anoxia, they significantly improved their survival. This regenerative capability was at least partly achieved through miR-514A-3p and SHP-2 and it decreased in hOMSC exposed to neural cells for 14 or 28 days. In addition, the beneficial effect of hOMSC were also confirmed in mice affected by stroke. Hence, in this work we have confirmed that hOMSC, in a time-limited manner, improve the survival of anoxia-damaged neurons and significantly contribute to the recovery of experimental animals following stroke., (© 2022. The Author(s).)

Objectives: This study evaluates the impact of systemic medications and polypharmacy on unstimulated (UWS) and chewing-stimulated whole saliva (SWS) flow rates in patients with xerostomia., Material and Methods: This cross-sectional multicenter study is based on data of patients referred to five oral medicine outpatient practices in Europe and USA from January 2000 and April 2014. Relevant demographic, social, medical history and current medications were collected., Results: The study included 1144 patients, 972 (85%) females, with a mean (SD) age of 59 (14.1) years. In unmatched patients, the UWS flow rate was lower in patients taking a medication (vs. not taking a medication) from the following drug categories: opioid analgesics, anticonvulsants, antidepressants, antihypertensives, benzodiazepines, corticosteroids, diuretics, disease-modifying antirheumatic drugs (DMARDs) and hormones. There was a greater negative effect on SWS flow rate in patients taking (vs. not taking) anticonvulsants, antidepressants, benzodiazepines, corticosteroids, and DMARDs. In matched patients, both UWS (0.22 vs. 0.19 ml/min; p = 0.03) and SWS (0.97 vs. 0.85 ml/min; p = .017) flow rates were higher in patients on non-opioid analgesics (vs. not taking). The UWS flow rate was lower in patients taking antidepressants (vs. not taking) (0.16 vs. 0.22 ml/min p = .002) and higher (and within normal range) in patients taking sex hormones (vs. not taking) (0.25 vs. 0.16 ml/min; p = .005). On the other hand, SWS was lower in patients taking corticosteroid (vs. not taking) (0.76 vs. 1.07 ml/min; p = .002), and in patients taking DMARDs (vs. not taking) (0.71 vs. 0.98 ml/min; p = .021). Finally, differences in medians of both UWS and SWS were statistically significant in patients taking 1 or more than 1 opioid analgesic (vs. not taking, p ≤ .0001 and p = .031, respectively), 1 or more than 1 anticonvulsants (vs. not taking, p = .008 and p = .007), 1 or more than 1 antidepressants (vs. not taking, p < .0001 for both), 1 or more than 1 DMARDs (vs. not taking, p = .042, and p = .003)., Conclusions: A greater negative impact on UWS and SWS flow rates was seen in patients taking more than one medication from the same drug class. Intake of antidepressants, corticosteroids and DMARDs is associated with lower whole saliva flow rates., Clinical Relevance: Salivary flow rate can be modified by some specific medications, mostly by polypharmacy., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The objective of this study was to assess the attitude, practice, and knowledge of Croatian dentists regarding infective endocarditis (IE) prophylaxis., Material and Methods: A cross-sectional, self-reporting questionnaire survey was conducted with the participation of 348 Croatian dentists. The questionnaire was designed to collect information on participants' work experience, place of work, their attitudes related to the treatment of IE-risk patients, knowledge and adherence to IE antibiotic prophylaxis guidelines., Results: Knowledge and adherence to the current guidelines decreased with the higher years of experience. Compliance with the current guidelines varied, mostly because of respondents' insecurity regarding which guidelines to follow. AHA guidelines have been most frequently the first choice (25% participants). Surprisingly, 23% of dentists didn't follow any of the official guidelines. The majority of participants (68%) have declared a lack of preparedness or willingness to treat the patients at risk of IE. Dentists with specialty or working at university/hospital have shown a higher level of knowledge and preparedness to treat IE-risk patients., Conclusions: The lack of knowledge of guidelines and consequent inconsistencies in IE antibiotic prophylaxis in Croatian dental practice indicates the need for urgent improvement. Key words: Antibiotic prophylaxis, dentistry, infective endocarditis., Competing Interests: Conflicts of interest None. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright: © 2021 Medicina Oral S.L.)

Drug-induced gingival overgrowth (DIGO) is a pathological growth of gingival tissue, primarily associated with calcium channel blockers and immunosuppressants. Consequently, it is mainly seen in cardiovascular and transplanted patients. Nifedipine remains the main calcium channel blocker related to the development of this unpleasant side-effect. As for immunosuppressants, cyclosporin is the leading causative agent, whereas other drugs from this drug-group, including tacrolimus, have better safety profiles. Accumulated collagen with inflammatory infiltrates is the histological hallmark of this condition. Several factors are involved in the pathogenesis and can increase the risk, such as male gender, younger age, pre-existing periodontal inflammation, and concomitant use of other DIGO-inducing medications. Patients with DIGO may experience severe discomfort, trouble with speech and mastication, pain, and teeth loss, aside from cosmetic implications. Furthermore, these patients also have an increased risk for cardiovascular diseases. The interdisciplinary approach and cooperation with dental care experts are necessary for patient management. Treatment includes discontinuing the drug and switching to one with a better profile, improving oral hygiene, and surgical removal of enlarged tissue. Recognizing the potential of commonly used medications to cause DIGO and its effect on patients' health is necessary for early detection and adequate management of this complication., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Aim: To evaluate the effectiveness of non-aromatic very rich in steranes (NAVS) naphthalan in the treatment of oral lichen planus (OLP) and recurrent aphthous stomatitis (RAS). Null hypothesis was that there would be no difference between NAVS and topical steroids in the treatment of OLP and RAS., Methods: The study consisted of two sub-trials conducted as randomized, double-blind controlled studies: first included OLP patients and second patients with RAS. Patients received either NAVS or 0.05% betamethasone dipropionate. Primary outcomes were activity score (OLP patients), No of lesions and lesion diameter (RAS patients) and pain intensity (VAS) while secondary outcome included the impact of the disease on quality of life assessed by Oral health impact profile (OHIP 14)., Results: No significant differences in terms of OLP clinical signs (p = 0.84, η2 = 0.001) and responses on the OHIP-14 (p = 0.81, η2 = 0.002) or on VAS (p = 0.14, η2 = 0.079) between NAVS and betamethasone groups were observed. In RAS patients, no significant differences between the groups in terms of lesion number (at days 3 and 5, p = 0.33 and p = 0.98, respectively), lesion diameter (days 3 and 5, p = 0.24 and p = 0.84, respectively) were observed. However, in NAVS group a significant reduction of lesions diameter was observed on the 3rd day, while in betamethasone group a significant reduction in lesions diameter was evident only after the 5th day. No significant differences in VAS (p > 0.05) and the OHIP-14 (p > 0.05) between groups were found., Conclusion: No evidence of differences between the two compared interventions was found., Registration: Retrospective registration of this trial was conducted in ClinicalTrials.gov on September 30, 2016; trial registration number: NCT02920658. https://clinicaltrials.gov/ct2/show/NCT02920658?term=NAVS&draw=2&rank=4., Competing Interests: The authors have declared that no competing interests exist.

Objective: To evaluate stress effect of COVID-19 pandemic and Zagreb earthquakes on symptoms of temporomandibular disorders (TMD)., Materials and Methods: One hundred and two previously diagnosed TMD patients were contacted by email to participate in an online survey about impact of those events on current and/or new symptoms, perceived stress, anxiety and symptom intensity in time-points at the baseline, following pandemic and following earthquake. We compared data between earthquake-affected and non-affected respondents., Results: Response rate was 79.4%. Effects stress had on deterioration of symptoms were significantly different between earthquake-affected and non-affected (p = .024). In earthquake-affected, numerical pain rating scale (NPRS) scores significantly increased between baseline and after COVID-19 (p > .001) and between baseline and after earthquakes (p > .05). However, scores insignificantly dropped from COVID-19 to after earthquakes time-points. In earthquake-affected, positive correlation was found between impact of COVID-19 on stress and NPRS (p < .001) and between earthquakes' impact on stress and NPRS (p < .001). Earthquake-affected respondents reported significantly more new behavioral habits when compared to non-affected (p = .048)., Conclusions: A series of stressful events do not necessarily have a cumulative effect, but are likely to have a complex interaction (e.g., acute stress might trigger the protective mechanisms), which could have decreased pain scores after the earthquakes., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.)

Temporomandibular disorders (TMD), when progress to a chronic state, might contribute to psychosocial or psychological distress. This study aimed to evaluate the effect of stabilization splint (SS) therapy on pain, pain-related disability and psychological traits of chronic TMD patients, as well as to assess selected oxidative stress (OS) biomarkers during 6-month treatment and associate them with the symptoms of anxiety and depression. Thirty-four participants were randomly assigned into two treatment groups [SS and placebo splint (PS)]. Primary outcomes were pain intensity and pain-related disability while secondary outcomes included depressive and anxiety symptoms. The influence of the treatment type was analyzed with regards to the levels of OS biomarkers in saliva. Participants treated with SS demonstrated significantly greater improvement in pain-related disability (Pain-free mouth opening: p = 0.018, η 2  = 0.166; Number of disability days: p = 0.023, η 2  = 0.155) and greater reduction of depressive symptoms scores (p = 0.007, η 2  = 0.207). When compared to the PS group, participants in the SS group showed a significant reduction of oxidant/antioxidant ratio (p = 0.018, η 2  = 0.167) at a 3-month follow-up. A stabilization splint provides advantages over PS in the treatment of depressive symptoms and pain-related disability. Furthermore, clinical success in terms of reduction of depressive symptoms, which correlates with the reduction of oxidative stress markers in the SS group, indicates that oxidative stress is related to psychological factors in chronic TMD patients.

Antibiotic prophylaxis (AP) of infective endocarditis (IE) in dental practice is a controversial topic. We evaluated the characteristics of the odontogenic IE and assessed the practice and sources of information pertaining to the topic utilized by the Croatian dentists. We conducted a retrospective review of consecutive medical charts of adult patients with IE, admitted to the University Hospital for Infectious Diseases in Zagreb, Croatia, between January 2007 and December 2017. In addition, a cross-sectional, self-reporting questionnaire survey was conducted with participation of 348 Croatian dentists. Of the 811 admissions for suspected IE (40.3% of all Croatian and 92.1% of all Zagreb hospitals), 386 patients were confirmed as definite IE: 68 with odontogenic IE and 318 with IE of other origin. Their first hospital admissions were analyzed. Definite odontogenic IE was defined as a positive echocardiographic result in conjunction with two separate positive blood cultures showing exclusive oral cavity pathogen or Streptococcus viridans associated with current or recent (< 1 month) dental, periodontal, or oral cavity infection. The annual number of new odontogenic IE patients appeared constant over time. In 91.2% of the cases, odontogenic IE was not preceded by a dental procedure; poor oral health was found in 51.5% of patients, and 47.1% had no cardiac condition that increases the IE risk. In-hospital mortality was 5.1% with conservative treatment and 4.5% with cardiac surgery and was much lower for odontogenic IE than in non-odontogenic IE (14.6% and 34.4%, respectively). An increasing number of admissions for non-odontogenic IE were observed in parallel with an increasing number of staphylococcal IE. Surveyed dentists (500 invited, 69.6% responded) were aware of the AP recommendations, but were largely reluctant to treat patients at risk. In people with poor oral health, AP should be considered regardless of cardiac risk factors. Improvement of oral health should be the cornerstone of odontogenic IE prevention.

Temporomandibular disorders (TMD) have been associated with altered salivary oxidative status, but the relation with pain source and pain severity isn't clarified. With the aim to assess their interaction with TMD, we compared levels of selected salivary oxidative stress (OS) markers (glutathione peroxidase, superoxide dismutase, total antioxidant capacity (TAC), uric acid, 8-hydroxydeoxyguanosine, malondialdehyde) and salivary cortisol (SC) as a stress indicator, between 20 TMD patients and 15 healthy control subjects. In order to record differences relating to pain source and severity, patients were respectively classified according to specific diagnoses (myofascial pain or disc displacement (DD)), and pain intensity (high or low). TAC was significantly higher in TMD patients than in controls (morning p = 0.015; afternoon p = 0.005). Significant differences were also observed when TAC levels between high-intensity pain patients and controls were compared, as well as between DD patients and controls. In logistic regression analysis, higher levels of TAC were related to DD (morning OR: 1.66, 95%CI: 1.05-2.64, p = 0.029; afternoon OR: 2.10, 95%CI: 1.11-3.98, p = 0.021) and to high-intensity pain (morning OR: 1.81, 95%CI: 1.04-3.15, p = 0.037; afternoon OR: 1.79, 95%CI: 1.02-3.14, p = 0.043). We also found that morning SC was positively correlated with antioxidant parameters in TMD patients. Our data suggest compensatory mechanism as response to higher level of stress. This stress could be extrinsic and lead toward TMD, or intrinsic, emerging from established TMD, or could be both. The intensity and the source of pain should be considered important factors in future investigations evaluating salivary OS markers in TMD patients.

Objectives: Opiorphin is a pentapeptide isolated from human saliva that suppresses pain from chemically induced inflammation and acute physical pain. Burning mouth syndrome (BMS) is a chronic condition of a burning sensation in the mouth, where no underlying dental or medical cause can be identified. We aimed to measure the level of opiorphin in whole unstimulated (UWS) and stimulated (SWS) saliva of patients with BMS., Materials and Methods: Originally developed and validated LC-MS/MS method was used for opiorphin quantification. Samples were obtained from 29 BMS patients and 29 age- and sex-matched controls., Results: The average concentration of opiorphin in UWS and SWS in the BMS group was 8.13 ± 6.45 and 5.82 ± 3.59 ng/ml, respectively. Opiorphin in BMS patients' UWS was significantly higher, compared to the control group (t = 2.5898; p = 0.0122). SWS opiorphin levels were higher, but not significantly, in BMS patients than in controls., Conclusions: Our results indicate that higher quantities of salivary opiorphin in BMS may be a consequence of chronic pain, but we cannot exclude that they occur as a result of emotional and behavioral imbalances possibly associated with BMS. To our knowledge, this is the first original article measuring opiorphin in a pain disorder., Clinical Relevance: Opiorphin may be a measurable biomarker for chronic pain, which could help in objectifying otherwise exclusively a subjective experience. Increased opiorphin could serve as a universal objective indicator of painful conditions. Since opiorphin may also reflect emotional and socio-relational imbalances occurring with BMS, it could as well represent a biomarker for BMS. Knowledge on opiorphin's involvement in pain pathways could contribute to developing new clinical diagnostic methods for BMS.

The present study evaluated diurnal variations and day-to-day fluctuations of salivary oxidative stress (OS) markers in healthy adult individuals. Whole unstimulated saliva was collected at 2 time intervals over 3 consecutive days. Glutathione peroxidase (GPX), superoxide dismutase (SOD), total antioxidant capacity (TAC), and uric acid (UA) were analyzed using spectrophotometric methods, while 8-hydroxydeoxyguanosine (8-OHdG) and malondialdehyde (MDA) were determined using immunoassays. No significant differences for salivary OS markers between men and women were observed. For all examined OS markers, no significant day-to-day variations were demonstrated. Significant diurnal variations were found in salivary GPX, TAC and MDA levels. For SOD, TAC, GPX, and UA, good-to-moderate intraindividual coefficients of variations (CVs) were observed in more than 75% of the subjects. For MDA and 8-OHdG, intraindividual CVs > 35% were observed in 60% and 40% of the subjects, respectively. Between-subject variance was wide for all examined OS markers (CV% 30.08%-85.70%). Due to high intraindividual variability in the salivary concentrations of MDA and 8-OHdG, those markers cannot be reliably verified based on single measurements and multiple measurements over several days would provide more reliable information. Salivary SOD, TAC, GPX, and UA proved stable across three days of measurement. Trial Registration . ClinicalTrials.gov NCT03029494. Registered on 2017-01-19.

Oral medicine (stomatology) is a recognized and increasingly important dental specialty in many parts of the world that recognizes and fosters the interplay between medical health and oral health. Its dental activities rely greatly on the underlying biology of disease and evidence-based outcomes. However, full recognition of the importance of oral medicine to patient care, research, and education is not yet totally universally acknowledged. To address these shortcomings, we outline the birth, growth, and future of oral medicine globally, and record identifiable past contributions to the development of the specialty, providing an accurate, unique, and valuable resource on oral medicine. Although it was challenging to gather the data, we present this information as a review that endeavors to summarize the salient points about oral medicine, based on MEDLINE, other internet searches, communication with oral medicine and stomatological societies across the world, the web page http://en.wikipedia.org/wiki/List&#95;of&#95;dental&#95;organizations, and discussions with a wide range of key senior persons in the specialty., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Electrical impedance is the resistance to the electric current flow through a tissue and depends on the tissue's structure and chemical composition. The aim of this study was to map electrical impedance spectra for each region of the healthy oral mucosa., Materials and Methods: Electrical impedance was measured in 30 participants with healthy oral mucosa. Measurements were performed in 14 points on the right and the left side of the oral cavity, and repeated after 7 and 14 days respectively., Results: The lowest values were measured on the tongue dorsum and the highest values were measured on the hard palate. No significant differences were found between the right and the left side. Significantly higher values were found in females on the upper labial mucosa, tongue dorsum and the ventral tongue. Significant difference between smokers and non-smokers on the lower labial mucosa and floor of the mouth was found. Electrical impedance was negatively correlated with salivary flow on the upper labial mucosa, hard palate, tongue dorsum and sublingual mucosa. Higher variability of measurements was found at low frequencies., Conclusions: Electrical impedance mostly depends on the degree of mucosal keratinization. Demographic and clinical factors probably affect its values. Further studies with bigger number of participants are required.

Objective: This systematic review aimed to (1) explore the patient-reported outcome measures (PROMs) currently used in the oral mucosal disease literature and report on the type and context of the use of these instruments and (2) provide a future direction for PROMs in Oral Medicine practice and research., Study Design: A systematic review of published English-language articles relating to the use of PROMs in the oral mucosal diseases literature was performed in November 2013., Results: In total, 131 articles met the inclusion criteria; these articles addressed the following oral mucosal conditions: lichen planus (75); recurrent aphthous stomatitis (30); mucous membrane pemphigoid/pemphigus vulgaris (14); orofacial granulomatosis (1); and multiple oral mucosal diseases (11). The most commonly used instruments were visual analog scales (VAS) and the oral health impact profile (OHIP)., Conclusions: Limited progress has been achieved with use of PROMs in Oral Medicine in the last few decades in both clinical practice and a research setting. With the engagement of allied medical disciplines in PROM usage and the promotion of PROMs by national health care bodies globally, advancement of PROMs is imperative for Oral Medicine. Exposure through the World Workshop on Oral Medicine (WWOM), along with potential involvement in the Core Outcome Measures in Effectiveness Trials (COMET) or other such initiatives, will enable worldwide collaboration to promote the development and utilization of valid and reliable PROMs in oral medicine, and improve patient care., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: The aim of the present study was to compare the efficiency of oral spray based on thermal spring water (Buccotherm®) versus commercial saliva substitute (Xeros®) and marshmallow root on the quality of life in patients with hyposalivation., Materials and Methods: A total of 60 patients with unstimulated salivary flow rate <0.2 ml/min were randomized into three groups. In the first group, 30 patients were using Buccotherm®; in the second group, 15 patients were using Xeros®; and in the third group, 15 patients were using marshmallow root. Therapy lasted for 2 weeks; everyday, patients used one of the products four times a day. Quality of life was measured by the Croatian version of Oral Health Impact Profile 14 questionnaire, and visual analog scale was used to determine the intensity of dry mouth before and after therapy. Statistical analysis was performed by Wilcoxon signed-rank test and Kruskal-Wallis test. Standardized effect size was calculated for OHIP following treatment., Results: Buccotherm® has shown the biggest effect on quality of life in patients with hyposalivation. Intensity of dry mouth was lower after the applied therapy whatever substitute patients used., Conclusions: We recommend the use of all three saliva substitutes for decreasing the intensity of dry mouth symptoms as well as improvement in the quality of life., Clinical Relevance: Although all tested agents showed beneficial effect in alleviating hyposalivation symptoms, it seems that Buccotherm® was superior to Xeros® and marshmallow root.

Stabilization splint is the treatment of choice for pain control in temporomandibular disorder (TMD) patients, even though its mechanism of action is still unknown. The aim of this systematic review is to provide a critical overview of the effectiveness of stabilization splint therapy on the basis of currently available literature data. The available Medline database was searched and 24 studies published since the 1995s have been consequently included in this review. The selection criteria were randomized controlled trials and clinical trials comparing splint therapy to either no treatment or another active treatment (physiotherapy, relaxation and drugs). Studies were grouped according to treatment type. Based on the currently best evidence available, it appears that stabilization splint has similar efficacy in controlling TMD symptoms as other active treatments (physiotherapy, relaxation and drugs). Stabilization splint therapy may be beneficial in reducing pain at rest and on palpation when compared with non-occluding splint. During a short period, education was slightly more effective than occlusal splint in treating spontaneous muscle pain. These two treatments did not have significantly different effects on pain-free mouth opening and pain during chewing. This review has shown evidence that most TMD patients are helped by incorporation of a stabilization splint. There is not enough data on the long-term efficacy and effectiveness of this widely used therapeutic tool. In the future, there is a need for well-conducted randomized controlled trials paying attention to adequate sample size, blind outcome assessment, duration of follow up, and using standardized methods for measuring treatment outcomes.

Aims: Sagittal condylar inclination is an important parameter during fabrication of prosthetic restorations. Existing data about intraindividual variations of sagittal condylar inclination are scarce. The purpose of this study was to investigate intra- and interindividual variations of the sagittal condylar inclination, depending on the position of the condyle in the temporomandibular joint., Methodology: The study included 51 subjects with Angle's Class I occlusion (21-32 years of age, mean 25.1). Measurements were done using an electronic axiograph. After a paraocclusal tray was fixed in the mouth, every subject had to make three protrusive movements, from which the device's software calculated the mean left and mean right sagittal condylar path. The mean left and right condylar path of each subject was divided into three equal sequences, based on whole condylar path length. Condylar inclination values for the first, second and third movement sequences were calculated., Results: Results showed significant differences between movement sequences (P < 0.05). For the left joint, condylar inclination values in the first condylar movement sequence demonstrated, on the average, 14.4% higher values compared to the second movement sequence, and 39.2% higher values than in the third movement sequence. For the right joint, the first condylar movement sequence demonstrated, on the average, 15.8% higher values compared to the second movement sequence, and 41.5% higher values than the third movement sequence., Conclusions: Results suggest that condylar movement in the sagittal direction is not uniform. Mean left and mean right condylar inclination values do not necessarily describe the actual condylar path, nor do they give adequate information for articulator setup. Left-right side condylar inclination differences greater than 10 degrees can be considered as normal.

Purpose: To quantify changes in pH, buffering capacity and hydrogen carbonate, phosphate, protein and urea concentrations of stimulated saliva which occur during a 30-min measurement delay after saliva collection. The correlation between time-related chemical changes and changes of salivary pH and buffering capacity was assessed in order to explain the observed changes in salivary pH and buffering capacity., Materials and Methods: Stimulated saliva samples were collected from 30 volunteers after inducing salivation by chewing a piece of parafilm. Measurements of salivary variables were made immediately after saliva collection and again 30 min later, during which time the specimens were exposed to the atmosphere in collection cups at room temperature., Results: Postponement of measurements resulted in a significant increase in pH and a significant decrease of buffering capacity, phosphate and urea concentration. The results suggest that the time-related pH increase could primarily be attributed to loss of dissolved carbon dioxide from saliva, and confirm the importance of hydrogen carbonate in the neutralisation of hydrogen ions, but they do not support the principle of catalysed phase-buffering for the hydrogen carbonate buffer system in saliva. A decrease in phosphate and urea concentration affects salivary buffering capacity., Conclusion: This study emphasises the importance of the standardisation of measurement time when measuring salivary pH, buffering capacity, phosphate and urea concentrations following the collection of saliva in order to obtain comparable results. It also provides a partial explanation of the mechanisms underlying the observed changes of pH and buffering capacity over time.

Oral lichen planus (OLP) is an immunologically T cell-mediated disease caused by an unknown stimulus. Despite intensive investigation its pathogenesis still remains unknown. A few possible associations between OLP and certain diseases such as thyroid and malignant diseases as well as specific medication intake have been proposed in the literature with inconsistent findings. We aimed to investigate the profile of 163 Australian and 163 Croatian OLP patients with special regard to their systemic diseases, medication intake (with special regard to the drugs that metabolize through Cytochrome P450), OLP type and localization, as well as involvement of other body surfaces with lichen. We did not find any statistical significance with regard to the OLP presence and thyroid and malignant diseases. As expected, the reticular type of OLP was most prevalent, as well as involvement of the both buccal mucosas. There was no significant association with other oral diseases such as labial herpes. Simultaneous involvement of other body surfaces in patients with OLP does not seem to be prevalent. None of the medical conditions which were investigated had significant correlation with OLP neither in Australian nor in Croatian patients with OLP. Furthermore, the use of drugs which metabolize through Cytochrome P450 (CYP450) was not significantly correlated with OLP in either studied population. Therefore, we conclude that patients with OLP are not to be routinely screened for any systemic conditions.

"Non-Aromatic Very rich in Steranes" (NAVS) naphthalan is a purified natural oil derivative, abundant in steranes (geogenic "steroids"). The purpose of this study was to evaluate the effectiveness of NAVS in the treatment of oral lichen planus (OLP) and recurrent aphthous stomatitis (RAS). We used NAVS oil in adhesive paste in 11 patients with clinically and histologically proven OLP (open label), and in 7 patients with RAS (double blind randomized; topical betamethasone in adhesive paste used as control). The severity of the OLP lesions was objectively scored. The number and diameter of RAS lesions were assessed on days 0, 3, and 5. The intensity of pain and discomfort was determined using visual analogue scale (VAS) and "Oral health impact profile" (OHIP-14) before and after therapy. OLP cumulative activity scores on days 0 and 28 were 101.5 and 48.5, respectively (t=5.99; P=0.0001). Using NAVS for 28 days resulted in 52.2% overall clinical improvement. Cumulative OHIP-14 scores on days 0 and 28 were 210 and 142, respectively (t=5.65; P=0.0002). Out of a total of 7 patients with RAS, 4 of them were treated with NAVS and 3 with topical corticosteroids. There were no statistically significant differences in improvement rate between the two groups (lesion number (day 3 P=0.29; day 5 P=0.32); lesion diameter (day 3 P=0.64; day 5 P=0.74)). NAVS successfully reduced the clinical signs and symptoms of OLP, and reduced the number, diameter, and symptoms in patients with RAS, statistically comparable with corticosteroids.

Many believe that oral sex is safe sex and does not pose a risk of getting sexually transmitted diseases. Despite the prevalence of oral sex, the number of diagnosed oral and pharyngeal sexually transmitted infection is lower than that of anal and vaginal sex. Oral contact with the genitals can cause tiny micro traumas through which pathological microorganisms that are present in body fluids can come into contact and be transmitted. This article reviews the literature on the role of oral sex in the transmission of sexually transmitted diseases and the corresponding clinical presentation or oral diseases.

Objective: A previous sham-controlled multinational study demonstrated the short-term efficacy and safety for xerostomia treatment of an intraoral device that delivers electrostimulation to the lingual nerve. The objective of this study was to test the hypothesis that those beneficial effects would be sustained over an 11-month period., Study Design: The device was tested on a mixed sample of 94 patients with xerostomia in an open-label, uncontrolled, prospective multicenter trial. Statutory outcome assessments were done at 5th, 8th, and 11th months and analyzed by multiple comparisons., Results: Improvements achieved at month 5 from baseline were sustained throughout the follow-up period for the primary outcome, xerostomia severity, and the secondary outcomes resting whole salivary flow rate, xerostomia frequency, oral discomfort, and difficulties in speech, swallowing, and sleeping. No significant side effects were detected., Conclusions: The beneficial effects of a removable intraoral electrostimulating device were sustained for an 11-month period., (Copyright © 2012 Elsevier Inc. All rights reserved.)

We report a case of propolis allergy in an 18-year-old female patient. Medical history revealed self-prescribed topical use of propolis spray as a medication for gingival swelling caused by orthodontic molar bands. After 24 hours, the patient developed lip edema and erythema of the perioral skin accompanied by burning pain in her lips. Discrete erosions were present in the corners of her lips. Erythema of the right infraorbital region was also observed. The patient was prescribed betamethasone propionate cream two times daily. Complete recovery was observed after 10 days. Propolis allergy was confirmed by a patch test. We believe that the use of propolis for the treatment of oral diseases should be avoided due to sparse evidence of its efficacy and numerous cases of allergic reactions.

Objectives: The aim of study was to compare salivary and serum concentrations of interleukin 1 beta (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in patients with oral leukoplakia, oral cancer and healthy controls., Study Design: Eighty eight patients (28 with oral cancer, 29 leukoplakia, and 31 healthy controls) were included in this study. Cytokine concentrations were measured by commercial enzyme linked immunoassay., Results: Salivary IL-1β and IL-6 were significantly higher in oral cancer patients than in patients with leukoplakia and control group (p<0.05). No differences in concentrations of salivary TNF-α between either of the groups were observed. Serum concentrations of IL-1β were below level of detection in all but two participants. No significant differences between the groups were observed in serum concentrations of IL-6. Serum TNF-α was significantly higher in control subjects than in oral cancer patients., Conclusions: Patients with oral cancer have elevated levels of inflammatory cytokines in their saliva. Whether this elevation can be used for monitoring the malignant transformation of oral leukoplakia remains to be answered by further follow up studies.

Opiorphin, QRFSR-peptide, is a mature product of the PROL1 (proline rich, lacrimal 1) protein that showed beneficial effects in pain management, antidepressant-like actions as well as involvement in colonic motility and erectile physiology. Using opiorphin as a potential biomarker of different pathological states requires the development of robust and sensitive methods. We report a highly sensitive and specific liquid chromatography with tandem mass spectrometric detection (LC-MS/MS) analytical method for the analysis of opiorphin in human saliva. Quantification was based on multiple reaction monitoring using characteristic transitions (m/z 347/120 - as quantifying ion; 347/175 and 347/268 as qualifying ions). The assay was linear in the range of 0-110 ng/ml and the lower limit of quantification reached was 1.0 ng/ml. The intra-day precision and accuracy were between 2.7-5.6% and -2.3 to 3.2%, respectively. The inter-day precision and accuracy were between 10.8-13.7% and -11.0 to 52%, respectively. Mean recovery was 106% and mean matrix effect was 0.97. Opiorphin in TFA treated saliva samples was stable for at least 12h at room temperature and up to 30 days at -20°C. Opiorphin levels in human saliva samples collected from young healthy individuals ranged from 2.8 to 25.9 ng/ml., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Aim of the study was to evaluate the diagnostic performance of the Rose Bengal score test for Sjøgren's syndrome (SS), and to explore differences between other tests and examinations. All participants were examined, including (but not limited to) unstimulated (UWS) and stimulated (SWS) whole saliva, labial gland biopsy (LGB or focus score), ophthalmologic questionnaire (ocular surface disease index OSDI) and objective tests: Schirmer test 1 (Sch. 1), Schirmer test 2 (Sch.2), Tear Break-up Time (TBUT) test and Rose Bengal score (RBS). Data were analyzed using Mann Whitney U-test, Receiver Operating Characteristic analysis, with specificity and sensitivity calculations and Spearman's correlation test. ROC curves showed a poor diagnostic performance of TBUT and OSDI. Sch. 1, Sch.2 and LGB all exhibited a high diagnostic performance. RBS exhibited the best performance (sensitivity 100,00; specificity 100,00; AUC 1,000). Study reveals the scarce reliability of TBUT, OSDI and Sch.1, and emphasizes RBS as the test of choice in the SS diagnosis.

The aims were to obtain epidemiological and etiological data on xerostomia in cross section of Croatian population, and to evaluate adherence to "American European Consensus Group" (AECG) classification criteria for Sjögren's syndrome (SSj), in order to identify possible need for improvements in differential diagnosis of xerostomia. A retrospective study among patients seen at the Department of oral medicine for complaints of dry mouth was performed. Three hundred and ninety-five patients met inclusion criteria. A data base was formed, comprising epidemiological, clinical and sialometric data, immunological, scintigraphic, ultrasonographic and histopathological findings of salivary glands, coupled with drug intake listings. Descriptive statistics were used for data analysis. Objective salivary hypofunction was found in 74% of our patients. The most common probable cause of xerostomia was side effect of pharmacotherapy. SSj was diagnosed in 6.7% of patients with xerostomia, whereas in another 8% of patients Sjögren's syndrome was strongly suspected, but labial gland biopsy wasn't performed, indicating a lack of adherence to AECG criteria for SSj diagnosis. Application of AECG criteria in differential diagnosis of patients with dry mouth is mandatory, as well as educating general practitioners, dentists and patients on xerogenic side effects of pharmacotherapy.

Objective: To evaluate the efficacy and safety of an intraoral electrostimulation device, consisting of stimulating electrodes, an electronic circuit, and a power source, in treating xerostomia. The device delivers electrostimulation through the oral mucosa to the lingual nerve in order to enhance the salivary reflex., Methods: The device was tested on a sample of patients with xerostomia due to Sjögren's syndrome and other sicca conditions in a 2-stage prospective, randomized, multicenter trial. Stage I was a double-blind, crossover stage designed to compare the effects of the electrically active device with the sham device, each used for 1 month, and stage II was a 3-month open-label stage designed to assess the long-term effects of the active device. Improvement in xerostomia severity from baseline was the primary outcome measure., Results: A total of 114 patients were randomized. In stage I, the active device performed better than the sham device for patient-reported xerostomia severity (P<0.002), xerostomia frequency (P<0.05), quality of life impairment (P<0.01), and swallowing difficulty (P<0.02). At the end of stage II, statistically significant improvements were verified for patient-reported xerostomia severity (P<0.0001), xerostomia frequency (P<0.0001), oral discomfort (P<0.001), speech difficulty (P<0.02), sleeping difficulty (P<0.001), and resting salivary flow rate (P<0.01)., Conclusion: Our findings indicate that daily use of the device alleviated oral dryness, discomfort, and some complications of xerostomia, such as speech and sleeping difficulties, and increased salivary output. The results show a cumulative positive effect of the device over the period of the study, from baseline to the end of the trial.

Orofacial granulomatosis (OFG) is an uncommon disease, usually presenting as recurrent or persistent swelling of the soft tissues in the orofacial region, predominantly lips (cheilitis granulomatosa). The cause of this illness is unknown. OFG may also be part of the triad of Melkersson-Rosenthal syndrome (MRS) and some consider it a monosymptomatic form of MRS. We describe a case of a Croatian male patient with recurrent swelling limited to the upper lip for the past 6 years. After establishing the diagnosis, we performed intralesional triamcinolone injections (16 mg, twice on a weekly schedule), resulting in complete remission. OFG differential diagnosis and treatment modalities are discussed.

The aim of this study was to analyze microphthalmia-associated transcription factor (MITF) as a marker for the detection of circulating melanoma cells, determine its prognostic value in melanoma patients, and compare it with tyrosinase. Blood samples from 201 melanoma patients in all stages of the disease and 40 healthy volunteers were analyzed. RNA was isolated from mononuclear cell fraction of the blood and assayed by reverse transcription-PCR for the expression of MITF and tyrosinase. All samples from healthy volunteers were negative for both MITF and tyrosinase. Out of 201 blood samples from melanoma patients 32 were positive for MITF, 20 for tyrosinase, and four for both MITF and tyrosinase. Analysis of MITF as an additional marker to tyrosinase allowed for detection of circulating melanoma cells in a larger number of melanoma patients in comparison to tyrosinase analysis alone (48 vs. 20 positive). A positive value of MITF was associated with shorter progression-free (P=0.005) and overall survival (P=0.042). A positive value of tyrosinase was associated with shorter overall survival (P=0.012), whereas there was no significant association between the value of tyrosinase and progression-free survival. The value of MITF was selected with multivariate analysis as the independent prognostic factor for progression-free survival, whereas the only independent prognostic factor for overall survival was the stage of disease. This study has shown that MITF is a specific marker for detection of circulating melanoma cells that has a prognostic value in melanoma patients. Determination of MITF in addition to tyrosinase improved the detection of circulating melanoma cells in melanoma patients.