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Objectives: To investigate the role of oral lichen planus (OLP) on the long‐term prognosis of oral epithelial dysplasia (OED). Methods: Retrospective single‐centre cohort study using the 2007–2019 database of the Head and Neck Cancer and Oral Medicine units of University College London Hospital. The exposure of interest was the presence of OLP, and the prognostic outcomes included the development of new primary episodes of OED, progression to malignancy and mortality. Cox proportional hazard and Poisson regression models were performed. Results: A total of 299 patients, of whom 144 had OED arising on the background of OLP (OLP/OED) and 155 had OED without underlying OLP (non‐OLP/OED), were included. A pre‐existing diagnosis of OLP was significantly associated with a twofold increased risk of subsequent primary OED events (HR = 2.02, p = 0.04), which also developed faster (1.46 vs. 2.96 years, p = 0.04) and with more involvement of non‐cancer‐prone sites (p = 0.001) than in the non‐OLP/OED group. There was no difference between groups in the progression to malignancy or mortality. Conclusions: Oral lichen planus/OED patients are at higher risk of multiple episodes of primary OED, which can develop faster and at non‐cancer‐prone sites as compared to non‐OLP/OED individuals. Further research is needed to clarify the effects of OLP upon progression to OSCC and mortality. [ABSTRACT FROM AUTHOR]

Objective Diclofenac is an effective and well-tolerated nonsteroidal anti-inflammatory drug ( NSAID) frequently used in the treatment of acute pain. Marketed formulations for parenteral administration usually contain 75 mg/3 mL of diclofenac sodium, which provide limited dosing flexibility, and are usually given intramuscularly. Methods We present a randomized, double-blind, active comparator- and placebo-controlled, parallel-group phase III multicenter study, investigating efficacy and tolerability of a new 1 mL-volume formulation of diclofenac sodium (25, 50 or 75 mg) containing hydroxypropyl-β-cyclodextrin ( HPβCD) as a solubility enhancer. This low-volume formulation allows subcutaneous ( SC), in addition to intramuscular ( IM) administration. Patients developing moderate-to-severe pain (≥ 50 mm on Visual Analogue Scale) after third molar extraction under local anesthesia were randomized to one of the 4 SC injections: 25 mg diclofenac HPβCD ( n = 77), 50 mg diclofenac HPβCD ( n = 76), 75 mg diclofenac HPβCD ( n = 78), or placebo ( n = 75). Results Mean pain intensity difference at 1.5 hours postdose (primary endpoint) was higher in all diclofenac-treated groups than placebo group. The adjusted means (95% CI) were 36.5 (31.7 to 41.2) in diclofenac 25 mg group, 37.3 (32.6 to 42.1) in diclofenac 50 mg group, 37.7 (33.0 to 42.4) in diclofenac 75 mg group, and 12.3 (7.44 to 17.1) in placebo group. Both 25 and 50 mg doses of diclofenac produced significantly greater pain relief than placebo ( P < 0.001 in both comparisons). Conclusion Single SC doses of diclofenac HPβCD of 25 and 50 mg are effective and well tolerated for relieving pain compared with placebo. [ABSTRACT FROM AUTHOR]

Context It is sometimes claimed that self-assessment is inaccurate and that clinicians over-rate their performance. There is a need to find out why this should be. Is poor self-assessment caused by some clinicians' inability to accurately judge performance? Or does over-scoring result from a desire to convey a more favourable impression? Peer assessment is widely advocated and is said to be of benefit to both assessor and assessee. Methods In this study, we wanted to see if postgraduates were able to peer-assess and if this form of assessment was more reliable than self-assessment when compared with assessment by a trainer. We used checklist and global rating scales to evaluate surgical skills in removing a mandibular third molar tooth. Results There was no statistically significant difference between peer-assessed and trainer-assessed scores. We found that, on average, peer assessment (especially global rating scales) reflected trainer scores more accurately than self-assessment of surgical skills. Self-assessment scores were significantly higher on average than those given in peer assessment. Discussion Although peers and trainee surgeons came from the same group, the surgeons were more likely to over-score when measuring their own performances. The greatest variability (and over-scoring) between assessor and trainee surgeon appeared to occur in those with lower mean scores. Formative peer assessment may be a useful and less stressful mechanism for encouraging reflection. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this cross‐sectional study was to explore the structural validity and internal consistency reliability of General Anxiety Disorder‐7, Patient Health Questionnaire‐8, 15 and Jaw Functional Limitation Scale‐20 in patients with chronic pain of temporomandibular disorders. Materials and Methods: Validity and reliability were assessed in 129 patients diagnosed according to the diagnostic criteria for temporomandibular disorders. Structural validity was explored using factor analysis, and internal consistency by calculating Cronbach α. Results: Confirmatory factor analysis revealed a suitable 2‐factor model for Patient Health Questionnaire‐8, with Cronbach α of 0.89, and 0.86. One and 2‐factor models were suitable for General Anxiety Disorder‐7, with overall Cronbach α of 0.93 for the 1‐factor model, and 0.91 and 0.84 for both factors in a 2‐factor model. A 4‐factor solution was appropriate for Patient Health Questionnaire‐15, with Cronbach α of 0.72, 0.57, 0.71 and 0.73 for each factor separately. Exploratory factor analysis was conducted to explore the factor structure of Jaw Functional Limitation Scale 20, and a 3‐factor solution was appropriate. Conclusions: This study provides positive evidence of structural validity and internal consistency of these questionnaires in patients with pain of temporomandibular disorders. However, additional testing is required to explore further psychometric properties. [ABSTRACT FROM AUTHOR]

Introduction: The importance of the patients' clinical experience has been reinforced several times over the last decade by healthcare organisations and policy makers. Routine gathering of experience data can help in enhancing patient‐centred care and provide guidance to quality improvement schemes. Patient‐reported experience measures can help to that end. The aim of this study was to develop a patient‐reported experience measure to evaluate the experience of patients with temporomandibular disorders while receiving healthcare. Methods: Input from several sources was utilised to develop the tool; previous literature, patients with temporomandibular disorders, and experts in the field. A qualitative study was conducted following the COnsensus‐based Standards for the selection of health Measurement Instruments guidance to generate the items of the questionnaire, which subsequently underwent cognitive testing. Results: Seventeen patients took part in the qualitative study, in addition to six healthcare professionals. The preliminary questionnaire consisted of 28 questions with six response options. Conclusions: This patient‐reported experience measure is a brief tool to evaluate the clinical experience of patients with temporomandibular disorders. Patients' involvement ensured face and content validity of the questionnaire, in addition to the relevance, comprehensibility and comprehensiveness of the items. [ABSTRACT FROM AUTHOR]

Objectives: To explore the experiences of patients with temporomandibular disorders (TMDs) with the National Health Service and to discover their healthcare priorities when seeking treatment. Methods: Semi‐structured interviews were used. They were directed using a topic guide covering subjects such as initial visits in primary care, referrals to secondary care, and the effect on symptoms. The discussions were audiotaped and transcribed verbatim. Thematic analysis was utilised to analyse the data. Results: In total, 15 participants took part in three focus groups. Six themes were identified: "access to appropriate care", "organised and coordinated care", "receiving a diagnosis and enough information", "interaction with the clinical staff", "treatment strategies and having an 'action plan'" and "support and social networks". Conclusions: The participants gave accounts of the difficulties encountered in healthcare in general terms and specific to TMD. Most notable was the struggle to access appropriate care, receive a diagnosis and be understood. Our findings suggest that delays in delivering appointments with people of expertise may have caused the worsening of symptoms. However, when a pleasant experience was encountered, access to care was fast, the clinician was understanding and communication with the clinical team was good. These provided positive experiences and were appreciated by the patients. [ABSTRACT FROM AUTHOR]

Objectives: Oral dysesthesia (burning mouth syndrome) is characterized by a burning-like sensation of the oral mucosa. The etiology of this disorder is still unknown, however, associations with oral fungal carriage have been proposed and applied clinically. The aim of the this study was to compare oral Candida carriage in patients with oral dysesthesia with Candida carriage in patients with other commonly diagnosed oral diseases to clarify the relationship between Candida and oral dysesthesia.Subjects and Methods: In total, 441 patients in total including 79 patients diagnosed with oral dysesthesia were included in this study. A retrospective analysis of mycological investigations undertaken in patients with clinically diagnosed oral dysesthesia compared with other oral conditions was undertaken.Results: Oral carriage of Candida was found in 63.3% (50 of 79) of patients with oral dysesthesia. The frequency of carriage and oral load of Candida were not significantly increased in patients with oral dysesthesia relative to the other conditions assessed. Patients with clinical signs of fungal infection or xerostomia presented with increased carriage of Candida.Conclusion: There is no association between oral dysesthesia and the presence or load of oral Candida. [ABSTRACT FROM AUTHOR]

Objective: To preliminary evaluate the clinical effects of probiotics in individuals with symptomatic oral lichen planus and the possible mechanisms of action. Subjects and Methods: A group of 30 individuals with symptomatic oral lichen planus were recruited in a randomised double‐blind parallel group controlled (1:1) proof‐of‐concept pilot trial of probiotic VSL#3 vs placebo. Efficacy outcomes included changes in pain numeric rating scale, oral disease severity score and the chronic oral mucosal disease questionnaire. Adverse effects, home diary and withdrawals were assessed as feasibility outcomes. Mechanistic outcomes included changes in salivary and serum levels of CXCL10 and IFN‐γ and in oral microbial composition. Results: The probiotic VSL#3 was safe and well tolerated. We observed no statistically significant change in pain, disease activity, quality of life, serum/salivary CXCL10 or oral microbial composition with respect to placebo. Salivary IFN‐γ levels demonstrate a trend for a reduced level in the active group (p = 0.082) after 30 days of probiotic consumption. Conclusions: The present proof‐of‐concept study provides some weak not convincing indication of biological and clinical effects of probiotic VSL#3 in individuals with painful oral lichen planus. Further research in this field is needed, with the current study providing useful information to the design of future clinical trials. [ABSTRACT FROM AUTHOR]

Phosphate glass is continuing to gain more attention as potential bone substitutes. The ternary (P2O5-CaO-Na2O) is investigated in terms of both physical properties and biocompatibility by doping different percentages of SiO2 and TiO2. Two groups were prepared; the first has different percentages of TiO2 and SiO2, whereas the second group compositions have 5 mol% TiO2 and 5 mol% SiO2 being added to compensate the network-forming oxide P2O5 and the network-modifying oxide CaO. Density, mass loss, pH, DTA, XRD, and cation release experiments were performed to study the physicochemical properties of the compositions, while MG63 and hMS cells were used within in vitro cell culture to study their biocompatibility. Results showed that an increase in TiO2 content correlated with an increase in glass density, decreased mass loss, increased trend of Tg and Tm values, and Na+ and Ca2+ release in group 1. There was no improvement in the MG63 viability or the ability of hMSCs to differentiate into osteoblasts where TiO2 decreased in favour of SiO2. Furthermore, in group 2, 50P2O5–25CaO was less dense than 45P2O5–30CaO, degraded dramatically less, had lower Tg and Tm values and released less Na+ and Ca(2+). The synergistic effect of doping 5 mol% TiO2 and 5 mol% SiO2 increased the MG63 viability in both compositions and was found 45P2O5–30CaO to have promising results in terms of the ability of hMSCs to differentiate into osteoblasts. To conclude, substituting TiO2 in place of SiO2 improved the physical properties and the biocompatibility of (P2O5-CaO-Na2O) glass system, whereas doping 5 mol% SiO2 and 5 mol% TiO2 together in place of P2O5 and CaO had a synergistic effect in controlling their degradation rate and improving their biological responses. [ABSTRACT FROM AUTHOR]

Background: Pichia pastoris has emerged as an important alternative host for producing recombinant biopharmaceuticals, owing to its high cultivation density, low host cell protein burden, and the development of strains with humanized glycosylation. Despite its demonstrated utility, relatively little strain engineering has been performed to improve Pichia, due in part to the limited number and inconsistent frameworks of reported genomes and transcriptomes. Furthermore, the co-mingling of genomic, transcriptomic and fermentation data collected about Komagataella pastoris and Komagataella phaffii, the two strains co-branded as Pichia, has generated confusion about host performance for these genetically distinct species. Generation of comparative high-quality genomes and transcriptomes will enable meaningful comparisons between the organisms, and potentially inform distinct biotechnological utilies for each species. Results: Here, we present a comprehensive and standardized comparative analysis of the genomic features of the three most commonly used strains comprising the tradename Pichia: K. pastoris wild-type, K. phaffii wild-type, and K. phaffii GS115. We used a combination of long-read (PacBio) and short-read (Illumina) sequencing technologies to achieve over 1000X coverage of each genome. Construction of individual genomes was then performed using as few as seven individual contigs to create gap-free assemblies. We found substantial syntenic rearrangements between the species and characterized a linear plasmid present in K. phaffii. Comparative analyses between K. phaffii genomes enabled the characterization of the mutational landscape of the GS115 strain. We identified and examined 35 non-synonomous coding mutations present in GS115, many of which are likely to impact strain performance. Additionally, we investigated transcriptomic profiles of gene expression for both species during cultivation on various carbon sources. We observed that the most highly transcribed genes in both organisms were consistently highly expressed in all three carbon sources examined. We also observed selective expression of certain genes in each carbon source, including many sequences not previously reported as promoters for expression of heterologous proteins in yeasts. Conclusions: Our studies establish a foundation for understanding critical relationships between genome structure, cultivation conditions and gene expression. The resources we report here will inform and facilitate rational, organismwide strain engineering for improved utility as a host for protein production. [ABSTRACT FROM AUTHOR]