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Key Points Salivary stones or sialoliths are calcified concrements in the salivary glands, most frequently located in Wharton's duct of the submandibular gland. Salivary stones consist of a mineralised nucleus, surrounded by laminated layers of organic and inorganic substances. The management of salivary stones depends on the size and location of the stone. Salivary stones, also known as sialoliths, are calcified concrements in the salivary glands. Sialoliths are more frequently located in the submandibular gland (84%), than in the parotid gland (13%). The majority of the submandibular stones are located in Wharton's duct (90%), whereas parotid stones are more often located in the gland itself. Salivary stones consist of an amorphous mineralised nucleus, surrounded by concentric laminated layers of organic and inorganic substances. The organic components of salivary stones include collagen, glycoproteins, amino acids and carbohydrates. The major inorganic components are hydroxyapatite, carbonate apatite, whitlockite and brushite. The management of salivary stones is focused on removing the salivary stones and preservation of salivary gland function which depends on the size and location of the stone. Conservative management of salivary stones consists of salivary gland massage and the use of sialogogues. Other therapeutic options include removal of the stone or in some cases surgical removal of the whole salivary gland.

Classical trigeminal neuralgia (CTN) is a severe neuropathic pain in the distribution of one or more branches of the trigeminal nerve, which occurs in recurrent episodes, causing deterioration in quality of life, affecting everyday habits and inducing severe disability. The aim of this review is to give an overview of the current literature on pharmaceutical treatment options for CTN in the elderly. The first-line treatment for the management of CTN in adults is an antiepileptic—carbamazepine or oxcarbazepine. There is a lack of research on the use of antiepileptics in the elderly. This is a deficiency, as the use of antiepileptics raises a number of problems due to the polypharmacotherapy common in older patients. This can induce drug interactions due to co-morbidities and changes in pharmacokinetics and pharmacodynamics. Furthermore, the side effects of carbamazepine include central nervous system disturbances, such as a lack of balance, dizziness, somnolence, renal dysfunction and cardiac arrhythmias, which are poorly tolerated by the elderly. Unfortunately, the efficacy and safety of alternative treatment options have not been systematically evaluated. On the basis of the current literature, it is not possible to give an evidence-based recommendation for first-line pharmaceutical management of CTN specifically for the elderly.

Key Points Highlights that a wide variety in the incidence of oral manifestations has been described in patients with Crohn's disease. Demonstrates that Crohn's disease has negative effects on oral health and therefore patients need special attention from dental clinicians. Points out that oral manifestations may precede gastrointestinal symptoms and recognition can lead to early referral to a gastroenterologist, which is important especially in children 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.

Objective Bone grafting is an important surgical procedure to restore missing bone in patients with alveolar cleft lip/palate, aiming to stabilize either sides of the maxillary segments by inducing new bone formation, and in bilateral cleft cases also to stabilize the pre-maxilla. Polyphosphate (PolyP), a physiological polymer composed of orthophosphate units linked together with high-energy phosphate bonds, is a naturally existing compound in platelets which, when complexed with calcium as Ca-polyP microparticles (Ca-polyP MPs), was proven to have osteoinductive properties in preclinical studies. Aim To evaluate the feasibility, safety, and osteoinductivity of Ca-polyP MPs as a bone-inducing graft material in humans. Methods This prospective non-blinded first-in-man clinical pilot study shall consist of 8 alveolar cleft patients of 13 years or older to evaluate the feasibility and safety of Ca-PolyP MPs as a bone-inducing graft material. Patients will receive Ca-polyP graft material only or Ca-polyP in combination with biphasic calcium phosphate (BCP) as a bone substitute carrier. During the trial, the participants will be investigated closely for safety parameters using radiographic imaging, regular blood tests, and physical examinations. After 6 months, a hollow drill will be used to prepare the implantation site to obtain a biopsy. The radiographic imaging will be used for clinical evaluation; the biopsy will be processed for histological/histomorphometric evaluation of bone formation. Discussion This is the first-in-man study evaluating the safety and feasibility of the polyP as well as the potential regenerative capacity of polyP using an alveolar cleft model. Trial registration Indonesian Trial Registry INA-EW74C1N . Registered on 12 June 2020

Key Points A limited number of studies reported widely varying prevalence rates of oral signs and symptoms in patients with ulcerative colitis. The most pathognomonic oral sign is pyostomatitis vegetans, but also other abnormalities as oral ulcerations, caries and periodontitis are more frequently observed in patients with ulcerative colitis. Patients with ulcerative colitis need special attention from dental clinicians. 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.

BACKGROUND: For patients with surgical third molar removal, it is unknown what constitutes a clinically important change in patients’ visual analogue scale (VAS) reports of pain intensity. OBJECTIVES: To determine what constitutes a clinically important change in pain intensity on a VAS following surgical removal of the third molar. METHODS: The study population consisted of patients participating in three randomized trials. Patients were asked to rate their pain three times per day over a period of seven days on a 100 mm VAS after surgical removal of the third molar. Global Perceived Effect was measured on day 1 and day 7 and was used as the external criterion for assessing clinically important pain reduction. Global Perceived Effect scores of 6 (‘much improved’) or higher were classified as clinically ‘successful’, and scores of 5 (‘slightly improved’) or below were classified as clinically ‘unsuccessful’. For each trial, the mean absolute and relative changes in VAS scores were calculated for both ‘successful’ and ‘unsuccessful’ treatments. Sensitivity and specificity analyses were performed. RESULTS: The patients who reported ‘successful’ pain reduction showed a relative pain reduction of ≥69% and an absolute pain reduction >2.5 cm on the VAS, whereas patients who classified their pain reduction as ‘unsuccessful’ had a relative pain reduction of ≥18.5% and an absolute pain reduction <0.5 cm on the VAS. Furthermore, sensitivity and specificity analyses showed that a cut‐off point of ≥50% relative pain reduction exhibited the best balance of sensitivity and specificity. CONCLUSION: Relative pain reduction of ≥50% and an absolute pain reduction of ≥2.5 cm on the VAS were most accurate in predicting a successful pain reduction after a given treatment.

Osteosarcoma (OS) mostly affects children and young adults, and has only a 20%-30% 5-year survival rate when metastasized. We aimed to create dual-targeted (extracellular against EphA2 and intracellular against JNK-interacting protein 1 [JIP1]), doxorubicin (DOX)-loaded liposomes to treat OS metastatic disease. Cationic liposomes contained -[1-(2,3-dioleoyloxy)propyl]- , , -trimethylammonium methyl-sulfate (DOTAP), cholesterol, 1,2-dipalmitoyl- -glycero-3-phosphocholine (DPPC), and distearoyl-phosphatidylethanolamine-methyl-poly(ethylene glycol) (DSPE-mPEG) conjugate. EphA2 targeting was accomplished by conjugating YSA peptide to DSPE-mPEG. Vesicles were subsequently loaded with DOX and JIP1 siRNA. Characteristics assessment showed that 1) size of the bilayered particles was 109 nm; 2) DOX loading efficiency was 87%; 3) siRNA could be successfully loaded at a liposome:siRNA ratio of >24:1; and 4) the zeta potential was 18.47 mV. Tumor-mimicking pH conditions exhibited 80% siRNA and 50.7% DOX sustained release from the particles. Stability studies ensured the protection of siRNA against degradation in serum. OS cell lines showed increased and more pericellular/nuclear localizations when using targeted vesicles. Nontargeted and targeted codelivery caused 70.5% and 78.6% cytotoxicity in OS cells, respectively (free DOX: 50%). Targeted codelivery resulted in 42% reduction in the siRNA target, JIP1 mRNA, and 46% decrease in JIP1 levels. Our dual-targeted, DOX-loaded liposomes enhance toxicity toward OS cells and may be effective for the treatment of metastatic OS.

An antibacterial and pro-osteogenic coaxially electrospun nanofiber guided bone regeneration (GBR) membrane was fabricated to satisfy the complicated and phased requirements of GBR process. In this study, we synthesize dual-functional coaxially electrospun nanofiber GBR membranes by encapsulating parathyroid hormone (PTH) in the core layer and magnesium oxide nanoparticles (MgONPs) in the shell layer (MgONPs-PCL/PTH-PCL). Herein, the physicochemical characterization of MgONPs-PCL/PTH-PCL, the release rates of MgONPs and PTH, and antibacterial efficiency of the new membrane were evaluated. Furthermore, the pro-osteogenicity of the membranes was assessed both in-vitro and in-vivo. We successfully fabricated a coaxially electrospun nanofiber MgONPs-PCL/PTH-PCL membrane with the majority of nanofibers (>65%) ranged from 0.40~0.60μm in diameter. MgONPs-PCL/PTH-PCL showed outstanding antibacterial potential against (E. coli) and (S. aureus) through the release of MgONPs. We also discovered that the incorporation of MgONPs significantly prolonged the release of PTH. Furthermore, both the in-vivo and in-vitro studies demonstrated that high dosage of PTH promoted pro-osteogenicity of the membrane to improve bone regeneration efficacy with the presence of MgONPs. The new composite membrane is a promising approach to enhance bone regeneration in periodontitis or peri-implantitis patients with large-volume bone defects.

Every year, over 260,000 patients in the Netherlands are diagnosed with a traumatic fracture. Many patients are treated surgically and need postoperative treatment of pain. Research suggests postoperative pain is often under-treated, leaving a significant proportion of patients in moderate to severe postoperative pain. Specialized, evidence-based pain-management protocols offer patients the best possible pain management, and significantly reduce the risk of pain-related health complications. Our objective was to review the range of postoperative pain protocols that are currently being used to treat postoperative fracture pain within the Netherlands, and investigate whether a specialized, evidence-based protocol for treating postoperative fracture pain exists within this sample. A written request for the protocol currently being used for the treatment of postoperative pain following the surgical treatment of a fracture was sent to 101 Dutch hospital departments. The administration and dosage of pain medications used during postoperative pain management were then identified and summarized. Of the contacted hospitals, 57% sent in protocols; 45% of these were eligible for analysis. All of the departments sent a general or acute pain protocol rather than a specialized protocol for the treatment of postoperative pain associated with the surgical treatment of fractures. A total of 22 different analgesics were used for pain management in 135 different administration schemes. Paracetamol, diclofenac, and morphine were used in the majority of protocols. Medication was given via oral, rectal, intravenous, subcutaneous, intramuscular, and epidural routes, amongst others. No specialized, evidence-based protocols for the treatment of postoperative fracture pain were found in this Dutch sample. A wide variety of medications, dosages, and administration schemes were used to manage postoperative pain following the surgical treatment of a fracture. The importance of developing a clear, specialized, evidence-based protocol for the treatment of postoperative pain following fracture surgery is discussed.

Medline. Single or double blinded randomised controlled trials (RCTs), in patients suffering from orofacial pain disorders, with pain intensity as main outcome measure and antidepressants as treatment modality were included. Study quality was assessed using a 15-item checklist. Two independent investigators extracted the data and a qualitative summary was presented. Six trials were included; four studies were randomised placebo-controlled trials and two were randomised active-controlled trials. All six trials were of high quality according to the 15-item criteria. Because of the heterogeneity of treatment modalities and the low number of trials per disorder there was limited evidence to support the effectiveness of antidepressants in orofacial pain disorders. More randomised controlled trials are needed to come to a firm conclusion for the use of antidepressants for orofacial pain disorders.